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Cluster headache (CH) is an excruciating and debilitating primary headache disorder. The prevalence is up to 1.3%, and the typical onset is around age 30. Often misdiagnosed as migraine, particularly in children, the diagnosis rate of CH has been increasing among women. CH is characterized by intense unilateral pain and autonomic symptoms, significantly impacting patients' quality of life, mental health, and productivity.Genetic associations suggest a familial risk for developing CH, with lifestyle factors also potentially playing a role. The pathophysiology involves alterations in both central and peripheral nervous system, with the hypothalamus, trigeminocervical complex, and neuropeptides such as calcitonin gene-related peptide (CGRP) being implicated.Nonpharmacological treatments focus on patient education and lifestyle modifications, while pharmacological treatments include acute therapies such as oxygen and subcutaneous or nasal sumatriptan, as well as preventive therapies like verapamil, lithium, and CGRP monoclonal antibodies. Transitional options include oral corticosteroids and greater occipital nerve injections. Emerging interventional procedures offer new avenues for managing refractory cases. Noninvasive vagal nerve stimulation and occipital nerve stimulation show promise for both acute and preventive treatment. Careful consideration of safety profiles is crucial in specific populations such as pregnant patients and children.Current treatments still leave patients highly burdened by limited efficacy and side effects. Future research continues to explore novel pharmacological targets, interventional procedures, and the potential role of psychedelics in CH management. Comprehensive, multifaceted treatment strategies are essential to improve the daily functioning and quality of life for individuals with CH., (© 2024. The Author(s).)

Background: Triptans are potent 5-HT 1B/1D/1F receptor agonists used in migraine therapy, thought to act through peripheral mechanisms. It remains unclear whether triptans cross the blood-brain barrier (BBB) sufficiently to stimulate central 5-HT 1B/1D/1F receptors. This study investigates the disposition of eletriptan and sumatriptan in central nervous system (CNS) and peripheral nervous system (PNS) regions and predicts regional 5-HT 1B/1D/1F receptor occupancies at clinically relevant concentrations., Methods: Using the Combinatory Mapping Approach (CMA) for regions of interest (ROI), we assessed the unbound tissue-to-plasma concentration ratio (K p, uu, ROI ) in rats at steady state across CNS (hypothalamus, brain stem, cerebellum, frontal cortex, parietal cortex, striatum, hippocampus, whole brain, and spinal cord) and PNS (trigeminal ganglion and sciatic nerve) regions. We used K p, uu, ROI values to estimate unbound target-site concentrations and 5-HT 1B/1D/1F receptor occupancies in humans., Results: We observed heterogenous triptan transport across CNS and PNS regions with the highest extent of unbound drug transport across the blood-nerve barrier in the trigeminal ganglion (K p, uu, TG : eletriptan: 0.519, and sumatriptan: 0.923). Both drugs displayed restricted entry across the BBB (K p, uu, whole brain : eletriptan: 0.058, and sumatriptan: 0.045) combined with high inter-regional variability. We estimated near-complete receptor occupancy in the trigeminal ganglion, while lower occupancies were observed in the whole brain, irrespective of the drug or receptor subtype. For instance, eletriptan was predicted to achieve 84% 5-HT 1B receptor occupancy in the trigeminal ganglion and 37% in the whole brain at clinically relevant concentrations., Conclusions: This study suggests that despite low BBB transport, both eletriptan and sumatriptan achieve unbound concentrations sufficient to stimulate 5-HT 1B, 5-HT 1D , and 5-HT 1F receptors not only in the trigeminal ganglion, but also in the CNS. Further research is needed to determine whether central mechanisms contribute to triptan's antimigraine effect and/or side effects., (© 2024. The Author(s).)

Objective: To evaluate the pharmacodynamic (PD) and pharmacokinetic (PK) interactions between zavegepant and sumatriptan in healthy adults., Background: Zavegepant is a high-affinity, selective, small-molecule calcitonin gene-related peptide receptor antagonist administered as a nasal spray approved in the United States for the acute treatment of migraine. Triptans, including sumatriptan, are a different class of drugs for acute migraine treatment and are associated with a risk of increased blood pressure (BP). Hence, it is important to study the drug-drug interactions between zavegepant and sumatriptan due to potential coadministration in clinical settings., Methods: This was a Phase 1, single-center, partially blind, randomized, placebo-controlled, single-arm study. Eligible participants were males aged ≥ 18 and ≤ 40 years or females aged ≥ 18 and ≤ 50 years. On Day 1, participants received sumatriptan 2 × 6 mg subcutaneous injections (1 h apart) and were then randomized (6:1 ratio) to receive zavegepant 2 × 10 mg nasal spray (1 in each nostril) or placebo on Days 2 and 3. On Day 4, zavegepant or placebo was coadministered with sumatriptan after the second sumatriptan injection. BP, PK, and safety were evaluated at pre-specified time points., Results: Forty-two participants enrolled in the study received at least one dose of any treatment and were included in the safety analyses. Forty-one participants who completed the study were included in the BP and PK analyses. The mean (standard deviation) time-weighted average (TWA) of mean arterial pressure (MAP [sumatriptan + zavegepant 87.2 (6.8) vs. sumatriptan 86.9 (6.0)]), diastolic BP (DBP [sumatriptan + zavegepant 72.3 (6.8) vs. sumatriptan 72.1 (6.2)]), and systolic BP (SBP [sumatriptan + zavegepant 116.8 (10.2) vs. sumatriptan 116.2 (8.6)]) did not change following zavegepant and sumatriptan coadministration on Day 4 compared to sumatriptan alone on Day 1. Statistical comparisons of the TWA of MAP, DBP, and SBP between sumatriptan and zavegepant coadministration and sumatriptan alone were similar; the differences observed were 0.04 mmHg for MAP (90% confidence interval [CI]: -0.69, 0.77 mmHg), 0.00 mmHg for DBP (90% CI: -0.76, 0.76 mmHg), and 0.33 mmHg for SBP (90% CI: -0.97, 1.63 mmHg). Sumatriptan PK after sumatriptan and zavegepant coadministration versus sumatriptan alone was similar; the comparison ratios were 102.5% (90% CI: 100.7%, 104.2%) for AUC 0-inf and 104.1% (90% CI: 98.0%, 110.6%) for C max . A small difference in zavegepant PK exposure after sumatriptan and zavegepant coadministration versus zavegepant alone was not considered clinically relevant: the comparison ratios were 112.4% (90% CI: 103.4%, 122.3%) for AUC 0-24 and 96.7% (90% CI: 88.9%, 105.2%) for C max . Overall, 90% (38/42) of participants experienced ≥ 1 treatment-emergent adverse event that was mild or moderate in severity. All treatments were generally safe and well tolerated., Conclusion: Coadministration of zavegepant with sumatriptan was safe and without PD or PK interactions in healthy adults., (© 2024 Pfizer Inc and The Author(s). Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Objective: Our primary outcome was to determine the feasibility of patients with post-traumatic headache (PTH) keeping a daily headache diary and using sumatriptan as directed. Secondary outcomes include determining if sumatriptan is effective in aborting PTH and whether headache resolution is dependent on PTH phenotype., Background: PTH is prevalent and persistent after traumatic brain injury, yet there have been few studies evaluating the effects of pharmacological treatments in individuals with PTH., Methods: This is a single-arm, prospective, non-randomized phase 2 clinical trial registered at Clinicaltrials.gov (NCT01854385) and conducted from 2013 to 2017. Data analysis was completed in 2022. Of the 299 participants screened, 40 were enrolled in the study. Participants kept a headache diary documenting headache characteristics and severity. Headache characteristics were used to determine PTH phenotypes of migraine-like, probable migraine-like, or non-migraine-like. Participants reported whether sumatriptan was used for their headache, their response to the medication, if a second dose was taken, and their response to the second dose., Results: A total of 15 participants out of the 40 enrolled (mean [SD] age, 41.9 [14.2] years, and 53% [21/40] male), met the criteria for the use of sumatriptan, and completed all assessments. Average headache diary compliance rate for the final month of the study was 80% (372/465). While sumatriptan was used for only 19% (122/654) of all reported headaches, 72% (88/122) of those headaches resolved within 2 h of taking the medication. Resolution of headaches with sumatriptan was not significantly different among headache phenotypes (migraine-like: 22/38 [58%], probable migraine-like: 24/29 [83%], non-migraine-like: 6/15 [40%]; p = 0.154)., Conclusions: A daily headache diary is feasible for tracking headache symptoms. Preliminary results also suggest that sumatriptan, a migraine-specific medication, may be beneficial for the treatment of PTH of different clinical phenotypes. Future studies, such as a phase 3 clinical trial with a larger sample size, are needed to better understand the efficacy of sumatriptan in the treatment of PTH., (© 2024 American Headache Society.)

Coronavirus disease 2019 (Covid-19) is a pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). In Covid-19, there is uncontrolled activation of immune cells with a massive release of pro-inflammatory cytokines and the development of cytokine storm. These inflammatory changes induce impairment of different organ functions, including the central nervous system (CNS), leading to acute brain injury and substantial changes in the neurotransmitters, including serotonin (5-HT) and calcitonin gene-related peptide (CGRP), which have immunomodulatory properties through modulation of central and peripheral immune responses. In Covid-19, 5-HT neurotransmitters and CGRP could contribute to abnormal and atypical vascular reactivity. Sumatriptan is a pre-synaptic 5-HT (5-HT1D and 5-HT1B) agonist and inhibits the release of CGRP. Both 5-HT and CGRP seem to be augmented in Covid-19 due to underlying activation of inflammatory signaling pathways and hyperinflammation. In virtue of its anti-inflammatory and antioxidant properties with inhibition release of 5-HT and CGRP, Sumatriptan may reduce Covid-19 hyperinflammation. Therefore, Sumatriptan might be a novel potential therapeutic strategy in managing Covid-19. In conclusion, Sumatriptan could be an effective therapeutic strategy in managing Covid-19 through modulation of 5-HT neurotransmitters and inhibiting CGRP.

Objective: Traditional pain management pathways following craniotomy are predicated on opioids. However, narcotics can confound critical neurological examination, contribute to respiratory depression, lower the seizure threshold, and lead to medication habituation, dependence, and/or abuse. Alternative medications to better address postoperative pain while mitigating opioid-related adverse effects remain insufficiently studied. Preliminary studies suggest sumatriptan, a 5-HT (1B/1D) receptor agonist known to regulate dural vasoactivity and inflammation, may moderate pain following trigeminal microvascular decompression and chronic postcraniotomy headache. In this study, the authors evaluated the efficacy of sumatriptan to modulate pain and opioid requirements following craniotomy surgery., Methods: This was a single academic center, retrospective cohort study of 300 consecutive adult patients who underwent elective craniotomy surgery between 2015 and 2022. Patients were equally divided between a control and a sumatriptan cohort contingent upon administration of 6 mg of subcutaneous sumatriptan within 1 hour of surgery completion and prior to opioid administration. Postoperative opioid consumption at 6, 12, and 24 hours, as well as admission total, inpatient length of stay, and 30-day global reevaluation, were assessed., Results: Three hundred patients were included for analysis. Significant differences were seen in baseline hypertension (p < 0.01), hyperlipemia (p < 0.01), anxiety (p = 0.04), and operative time (p = 0.02). A significant reduction of mean postoperative pain scores at 12 (p = 0.03) and 24 (p < 0.01) hours and total opioid consumption (p = 0.04) was observed in the sumatriptan cohort. Subgroup analysis revealed significantly lower postoperative pain scores at 6 (p = 0.05), 12 (p < 0.01), and 24 (p < 0.01) hours in patients who underwent burr hole placement in the sumatriptan cohort as compared with controls; however, no significant difference in opioid consumption was noted. No adverse events related to sumatriptan administration were noted throughout the study., Conclusions: Postoperative single-dose subcutaneous sumatriptan following elective craniotomy may reduce pain scores and opioid requirements. Additional studies are needed to better understand nuanced differences in opioid modulation and optimal patient selection.

Chronic orofacial pain disorders are common debilitating conditions, affecting the trigeminal system. Its underlying pathophysiological mechanisms are still unclear and the therapy is often unsatisfactory, therefore, preclinical models are crucial to identify the key mediators and novel treatment options. Complete Freund's adjuvant (CFA)-induced orofacial inflammatory allodynia/hyperalgesia is commonly used in rodents, but it has not been validated with currently used drugs. Here we tested the effects of the adjuvant analgesic/antiepileptic voltage-gated Na + channel blocker complex mechanism of action topiramate in comparison with the gold standard antimigraine serotonin 5-HT1B/D receptor agonist sumatriptan in this model. CFA was injected subcutaneously into the right whisker pad of male Sprague-Dawley rats (250-300 g), then mechanonociceptive threshold values were investigated with von Frey filaments (3, 5, and 7 days after CFA injection). Effects of topiramate (30 mg/kg per os ) and sumatriptan (1 mg/kg subcutaneous ) on the adjuvant-induced chronic inflammatory orofacial allodynia were investigated 60, 120, and 180 min after the treatments each day. To determine the optimal concentration for drug effect analysis, we tested the effects of two different CFA-concentrations (1 and 0.5 mg/mL) on mechanonociceptive thresholds. Both concentrations of CFA induced a chronic orofacial allodynia in 60% of all rats. Although, higher CFA concentration induced greater allodynia, much more stable threshold reduction was observed with the lower CFA concentration: on day 3 the thresholds decreased from 18.30 g to approximately 11 g (low) and 5 g (high), respectively, however a slight increase was observed in the case of higher CFA concentration (on days 5, 7, and 11). In all investigation days, topiramate showed significant anti-allodynic effect comparing the pre and post drug dose and comparing the vehicle treated to the drug treated groups. Sumatriptan also caused a significant threshold increase compared to pre dose thresholds (day 3) and also showed a slight anti-allodynic effect compared to the vehicle-treated group (day 3 and 5). In the present study CFA-induced chronic orofacial allodynia was reversed by topiramate in rats validating the model with the adjuvant analgesic. Other than establishing a validated orofacial pain-related syndrome model in rats, new ways are opened for the repurposing of topiramate., Competing Interests: Authors TK and SF were employed by Uzsoki Cardiovascular Center Ltd. Authors EP and ZH were employed by PharmInVivo Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mohos, Harmat, Kun, Aczél, Zsidó, Kitka, Farkas, Pintér and Helyes.)

Around 91% of migraine patients use over-the-counter medicines to treat attacks, often without further treatment or medical consultation. This therapeutic principle is established in most countries, regardless of how the healthcare system is otherwise structured or financed. Using Germany as an example, the basis for an expansion of attack therapy with rizatriptan as an over-the-counter triptan is described. To achieve the best possible tolerability and safety in the context of self-medication, the lowest possible dose should be selected to provide the most favourable tolerability and safety profile in the context of self-medication through low dosages. The lowest approved dose of rizatriptan is 5 mg. This was investigated in three randomized controlled trials with 752 patients. The results show that rizatriptan at a dose of 5 mg is more effective than the triptans naratriptan 2.5 mg, almotriptan 12.5 mg and sumatriptan 50 mg, which were previously available for self-medication in Germany. There was no significant difference in the frequency of adverse events with rizatriptan 5 mg compared to placebo. Rizatriptan 5 mg does not have a higher side effect potential than sumatriptan 50 mg, which is already exempt from the prescription requirement. The reasons given show that rizatriptan in a dose of 5 mg for the treatment of acute migraine attacks fulfils the requirements for a transfer from prescription to pharmacy-only status at least as well as sumatriptan 50 mg, naratriptan 2.5 mg and almotriptan 12.5 mg. From a clinical care perspective, it is desirable for affected patients to have other options available for self-medication. Non-responders to other substances also have a further treatment option with rizatriptan 5 mg, with the same or even better risk-benefit profile, to treat migraine attacks safely, effectively and in a tolerable manner as part of self-medication., (© 2024. The Author(s).)

Background and Purpose: Sumatriptan protects the brain from damage and enhance the anti-seizure effect of morphine. There is evidence that nitric oxide (NO) may mediate these effects of both drugs. In the present study, we investigated the effects of sumatriptan (0.1-20 mg/kg, intraperitoneal [i.p.]) and morphine (0.1-20 mg/kg, i.p.) alone or in combination on seizure thresholds in an in vivo model of seizure in mice. Using various NO synthase inhibitors as well as the NO precursor, we assessed possible involvement of NO signaling in these effects., Methods: Clonic seizures were induced in male Naval Medical Research Institute mice by intravenous administration of pentylenetetrazol (PTZ)., Results: Acute sumatriptan administration exerted anti-convulsive effects at 0.5 ( p <0.01) and 1 mg/kg ( p <0.05), but pro-convulsive effects at 20 mg/kg ( p <0.05). Morphine had anti-convulsive effects at 0.5 ( p <0.05) and 1 mg/kg ( p <0.001), but exerted pro-convulsive effect at 20 mg/kg ( p <0.05). Combination treatment with sub-effective doses of sumatriptan (0.1 mg/kg) and morphine (0.1 mg/kg) significantly ( p <0.05) exerted an anti-convulsive effect. Co-administration of the NO precursor L-arginine (60 mg/kg) with sub-effective doses of sumatriptan and morphine significantly ( p <0.05) increased seizure threshold compared with sumatriptan alone, but not sumatriptan+morphine group. While concomitant administration of either the non-selective NO synthase (NOS) inhibitor L-N G -nitroarginine methyl ester (5 mg/kg) or the selective inducible NOS inhibitor aminoguanidine (50 mg/kg) with combined sub-effective doses of morphine and sumatriptan produced significant anticonvulsive effects, concomitant administration with the selective neuronal NOS inhibitor 7-nitroindazole (30 mg/kg) inhibited this effect., Conclusions: Our data suggest a possible role for the NO signaling in the anticonvulsive effects of combined sumatriptan and morphine on the PTZ-induced clonic seizures in mice., Competing Interests: The authors report no conflicts of interest related to the present study., (Copyright © 2024 Korean Epilepsy Society.)

Introduction  Postcraniotomy headaches are often underestimated and undertreaded. This study aimed to identify if postoperative administration of sumatriptan after minimally invasive craniotomy for clipping an unruptured aneurysm could reduce postcraniotomy headache and improve the quality of postoperative recovery. Settings and Design  Tertiary care center, single-center randomized double-blind placebo-controlled trial. Materials and Methods  Patients who complained of postoperative headaches after minimally invasive craniotomy for clipping of unruptured aneurysms were randomized to receive subcutaneous sumatriptan (6 mg) or placebo. The primary outcome was the quality of recovery measured 24 hours after surgery. Secondary outcomes were total opioid use and headache score at 24 hours after surgery. Data were analyzed using a Student's t -test or the chi-square test. Results  Forty patients were randomized to receive sumatriptan ( n  = 19) or placebo ( n  = 21). Both groups had similar demographics, comorbidities, and anesthesia management. The Quality of Recovery 40 score was higher for patients receiving sumatriptan compared to placebo, however, not statistically significant (173 [156-196] vs. 148 [139-181], p  = 0.055). Postoperative opioid use between sumatriptan and placebo was lower, but not significant (5.4 vs. 5.6 mg morphine equivalent, p  = 0.71). The severity of headache was also not statistically different between the two groups (5 [4-5] vs. 4 [2-5], p  = 0.155). Conclusion  In patients undergoing minimally invasive craniotomies for aneurysm clipping, sumatriptan given postoperatively has a nonsignificant trend for a higher quality of recovery. Similarly, there was a nonsignificant trend toward lower postcraniotomy headache scores and opioid scores for the patient given sumatriptan., Competing Interests: Conflict of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objectives: Research has demonstrated that chronic stress experienced early in life can lead to impairments in memory and learning. These deficits are attributed to an imbalance in the interaction between glucocorticoids, the end product of the hypothalamic-pituitary-adrenal (HPA) axis, and glucocorticoid receptors in brain regions responsible for mediating memory, such as the hippocampus. This imbalance can result in detrimental conditions like neuroinflammation. The aim of this study was to assess the impact of sumatriptan, a selective agonist for 5-HT 1B/1D receptors, on fear learning capabilities in a chronic social isolation stress model in mice, with a particular focus on the role of the HPA axis., Methods: Mice were assigned to two opposing conditions, including social condition (SC) and isolated condition (IC) for a duration of five weeks. All mice underwent passive avoidance test, with their subsequent freezing behavior serving as an indicator of fear retrieval. Mice in the IC group were administered either a vehicle, sumatriptan, GR-127935 (a selective antagonist for 5-HT 1B/1D receptors), or a combination of sumatriptan and GR-127935 during the testing sessions. At the end, all mice were sacrificed and samples of their serum and hippocampus were collected for further analysis., Results: Isolation was found to significantly reduce freezing behavior (p<0.001). An increase in the freezing response among IC mice was observed following the administration of varying doses of sumatriptan, as indicated by a one-way ANOVA analysis (p<0.001). However, the mitigating effects of sumatriptan were reversed upon the administration of GR-127935. An ELISA assay conducted before and after the passive avoidance test revealed no significant change in serum corticosterone levels among SC mice. In contrast, a significant increase was observed among IC mice, suggesting hyper-responsiveness of the HPA axis in isolated animals. This hyper-responsiveness was ameliorated following the administration of sumatriptan. Furthermore, both the sumatriptan and SC groups exhibited a similar trend, showing a significant increase in the expression of hippocampal glucocorticoid receptors following the stress of the passive avoidance test. Lastly, the elevated production of inflammatory cytokines (TNF-α, IL-1β) observed following social isolation was attenuated in the sumatriptan group., Conclusion: Sumatriptan improved fear learning probably through modulation of HPA axis and hippocampus neuroinflammation., Competing Interests: Declaration of Competing Interest This study was the postgraduate thesis of Dr Kamyar Moradi under the supervision of Prof. Ahmad Reza Dehpour. This study was supported by a grant from Iran National Science Foundation (INSF) to Prof. Ahmad Reza Dehpour (Grant Number: 96002757). The funding organization had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the article and the decision to submit the article for publication. To the best of our knowledge, no conflict of interest, financial or other, exists. I have read and have abided by the statement of ethical standards for manuscripts submitted to Psychoneuroendocrinology., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung condition that produces symptoms including coughing which may cause by excessive accumulation of scar tissue inflammatory and oxidative stress exacerbation. Sumatriptan, utilized for migraine treatment as a selective 5-HT 1B/1D receptor agonist, has demonstrated significant anti-inflammatory and antioxidant properties in multiple preclinical investigations. Operating primarily on serotonin receptors, sumatriptan leverages the diverse physiological functions of serotonin, playing a pivotal role in regulating both inflammation and oxidative stress which is particularly relevant in the context of IPF., Materials & Methods: Thirty-five male Wistar rats were divided to five group, including: Sham (without IPF induction), control (BLM 5 mg/kg, intraperitoneally), and three fibrosis group with sumatriptan (0.5, 1, and 3 mg/kg, i.p. for 2 weeks) administration. IPF was induced by injection of BLM (single dose, 5 mg/kg intratracheally). Lung tissues were separated for measurement of myeloperoxidase (MPO) as an oxidative stress hallmark, and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-β), and transforming growth factor-β (TGF-β) as inflammatory markers as well as alpha smooth muscle actin (α-SMA). Also, for histological investigations, tissue damages were assessed by Hematoxylin-eosin (H&E) and Masson's trichrome staining method., Results: BLM-induced fibrosis could increase α-SMA, MPO, TNF-α, IL-1β, and TGF-β, while treatment with sumatriptan has reversed the α-SMA, MPO, and IL-1β levels. Moreover, the results of H&E and Masson's trichrome staining indicated that sumatriptan (1 and 3 mg/kg) reduced tissue damages, alveolar wall thickness, collagen accumulation, and pulmonary fibrosis induced by BLM., Conclusion: According to the data achieved from this study, Sumatriptan appears to have therapeutic benefits in IPF, possibly via reducing α-SMA as well as inflammation and the toxicity caused by oxidative stress., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to test whether a combination of sumatriptan with dual enkephalinase inhibitor PL37 would result in an additive or a synergistic effect., Background: Combination treatment is frequently used to improve the therapeutic efficacy of drugs. The co-administration of two drugs may result in efficacy at lower doses than those needed for either drug alone, thus minimizing side effects. Here, we tested the effect of the co-administration of two drugs on cutaneous mechanical hypersensitivity (MH), a symptom often affecting cephalic regions in patients with migraine: dual enkephalinase inhibitor PL37, a small molecule that protects enkephalins from rapid degradation, and sumatriptan, a serotonin 5-HT 1B/1D receptor agonist., Methods: We investigated the effects of oral administrations of sumatriptan, PL37, or their combination on changes in cutaneous mechanical sensitivity induced by a single intraperitoneal administration of the nitric oxide donor, isosorbide dinitrate (ISDN) in male rats. Mechanical sensitivity was assessed using von Frey filaments applied to the face of animals to determine pain thresholds. Isobolographic analysis was performed to determine the nature of the interaction between sumatriptan and PL37., Results: Sumatriptan as well as PL37 each produced a dose-dependent inhibition of ISDN-induced cephalic MH. Median effective dose (ED 50 ) values were 0.3 and 1.1 mg/kg for sumatriptan and PL37, respectively. An isobolographic analysis of the effect of combined doses of sumatriptan and PL37 based on their calculated ED 50 values demonstrated a synergistic effect of the combination on cephalic MH, with an interaction index of 0.14 ± 0.04., Conclusion: These results suggest that PL37 acts synergistically with sumatriptan to produce an anti-allodynic effect in a rat model of migraine. Thus, combining PL37 and sumatriptan may be a useful therapeutic strategy in the management of migraine., Plain Language Summary: There have been many advances in migraine treatment, but we still need more options that are effective and have few side effects. Sumatriptan is one available drug for acute treatment of migraine, but it does not work for every patient and is not suitable for some people. We tested a new drug called PL37 (that blocks enkephalinases) together with sumatriptan and the combination minimized side effects and allowed lower doses of the drugs for effective migraine treatment in an animal model., (© 2024 American Headache Society.)

Background: Migraine and vestibular migraine are disorders associated with a heightened motion sensitivity that provoke symptoms of motion-induced nausea and motion sickness. VM affects ∼3% of adults in the USA and affects three-fold more women than men. Triptans (selective serotonin receptor agonists) relieve migraine pain but lack efficacy for vertigo. Murine models of photophobia and allodynia have used injections of calcitonin gene-related peptide (CGRP) or other migraine triggers, such as sodium nitroprusside (SNP), to induce migraine sensitivities in mice to touch and light. Yet, there is limited research on whether these triggers affect motion-induced nausea in mice, and whether migraine blockers can reduce these migraine symptoms. We hypothesized that systemic delivery of CGRP or SNP will increase motion sickness susceptibility and motion-induced nausea in mouse models, and that migraine blockers can block these changes induced by systemically delivered CGRP or SNP., Methods: We investigated two measures of motion sickness assessment [motion sickness index (MSI) scoring and motion-induced thermoregulation] after intraperitoneal injections of either CGRP or SNP in C57BL/6J mice. The drugs olcegepant, sumatriptan and rizatriptan were used to assess the efficacy of migraine blockers., Results: MSI measures were confounded by CGRP's effect on gastric distress. However, analysis of tail vasodilatations as a surrogate for motion-induced nausea was robust for both migraine triggers. Only olcegepant treatment rescued tail vasodilatations., Conclusions: These preclinical findings support the use of small molecule CGRP receptor antagonists for the treatment of motion-induced nausea of migraine, and show that triptan therapeutics are ineffective against motion-induced nausea of migraine. Trial Registration: Not Applicable., Competing Interests: Declaration of conflicting interestsThe authors declare that there are no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

In this study, the determination of sumatriptan (SUM) was performed using a simple, rapid, and precise colorimetric method based on the surface plasmon resonance (SPR) feature of gold nanoparticles (AuNPs). By adding SUM, the aggregation was observed in AuNPs with red-to-blue color shifts. The size distribution of NPs was estimated before and after adding SUM via dynamic light scattering (DLS), which was found to be 15.34 and 97.45 nm, respectively. Characterization of AuNPs, SUM, and AuNPs in combination with SUM was investigated using transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR). Examining the effect of pH, the volume of buffer, the concentration of AuNPs, interaction time, and ionic strength revealed that their optimal values were 6, 100 μL, 5 μM, 14 min, and 12 μg L -1 , respectively. The suggested method was able to determine the amount of SUM in a linear range of 10 to 250 μg L -1 with a limit of detection (LOD) and limit of quantification (LOQ) of 0.392 and 1.03 μg L -1 , respectively. This approach was successfully applied to determine SUM in drinking water, saliva, and human urine samples with relative standard deviations (RSD) lower than 0.03%, 0.3%, and 1.0%, respectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Migraine is a progressive neurological condition often accompanied by nausea and vomiting. Various drugs have recently been used in the treatment of migraine, including sumatriptan (SUT). However, SUT has poor pharmacological effects mainly due to its reduced permeability, blood brain barrier (BBB) effect, half-life and bioavailability. Herein, we developed SUT loaded nano-ethosomes (SUT-NEs) for intranasal (IN) delivery, after their incorporation into chitosan based mucoadhesive gel (SUT-NEsG). The observed mean particle size of SUT-NEs was 109.45 ± 4.03 nm with spherical morphology, mono dispersion (0.191 ± 0.001), negatively charged (-20.90 ± 1.98 mV) and with excellent entrapment efficiency (96.90 ± 1.85 %). Fourier-transform infrared (FTIR) spectra have depicted the compatibility of the components. Moreover, SUT-NEsG was homogeneous having suitable viscosity and mucoadhesive strength. In vitro release and ex vivo permeation analysis showed sustained release and improved permeation of the SUT-NEsG, respectively. Additionally, histopathological studies of nasal membrane affirmed the safety of SUT-NEsG after IN application. In vivo pharmacokinetic study demonstrated improved brain bioavailability of SUT-NEsG as compared to orally administered sumatriptan solution (SUT-SL). Furthermore, significantly enhanced pharmacological effect of SUT-NEsG was observed in behavioral and biochemical analysis, immunohistochemistry for NF-κB, and enzyme linked immuno assay (ELISA) for IL-1β and TNF-α in Nitroglycerin (NTG) induced migraine model. It can be concluded that migraine may be successfully managed through IN application of SUT-NEsG owing to the direct targeted delivery to the brain., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Fakhar Ud Din, PhD reports financial support was provided by Higher Education Commission Pakistan.]., (Copyright © 2023 Elsevier B.V. All rights reserved.)

An electrochemical sensory platform is presented for determination of sumatriptan (SUM) in aqueous solutions and human blood serum. A pencil graphite electrode (PGE) was electrochemically delaminated by cyclic voltammetry technique, and then further modified using nanoparticles of a zinc-based metal-organic framework (Zn(II)-MOF). The fabricated Zn(II)-MOF/EDPGE electrode was utilized for sensitive electrochemical detection of SUM via an electro-oxidation reaction. The Zn(II)-MOF was hydrothermally synthesized and characterized by various techniques. The electrochemical delamination of PGE results in a porous substrate, facilitating the effective immobilization of the modifier. The designed sensor benefits from both enhanced surface area and an accelerated electron transfer rate, as evidenced by the chronocoulogram and Nyquist plots. Under optimized conditions, the developed sensor exhibited a linear response for 0.99-9.52 µM SUM solutions. A short response time of 5 s was observed for the fabricated sensor and the detection limit was found to be 0.29 μM. Selectivity of Zn(II)-MOF/EDPGE towards SUM was evaluated by examining the interference effect of codeine, epinephrine, acetaminophen, ascorbic acid, and uric acid, which are commonly found in biological samples. The developed sensor shows excellent performance with recovery values falling within the range of 96.6 to 111% for the analysis of SUM in human blood serum samples., (© 2023. Springer Nature Limited.)

Background: Coronary artery spasm is a well-known potential side effect of selective 5-hydroxytryptamine type 1 (5HT1) receptor agonists and, therefore, contraindicated in patients with cardiovascular disease. SARS-CoV-2 vaccination has been associated with myocarditis, mainly in young men., Case Summary: A 55-year-old man with longstanding cluster headache, treated with the 5HT1-agonist Sumatriptan for ten years, received the mRNA-1273 SARS-CoV-2 booster vaccine. Four days later, he developed severe retrosternal pain several minutes after administering Sumatriptan with electrographic ST-elevation and a raised high-sensitivity cardiac troponin-T (hs-cTnT). Coronary angiogram was normal, but a diagnosis of acute myocarditis and hyperthyroidism secondary to Graves' disease was made., Discussion: We present a case of severe coronary artery spasm induced by a 5HT1-agonist secondary to newly diagnosed Graves' disease and myocarditis. The mRNA-1273 SARS-CoV-2 booster vaccine administered four days before admission probably triggered both immunoreactions.

Background: The management of cluster headache is similar to that of other primary headache disorders and can be broadly divided into acute and preventive treatments. Acute treatments for cluster headache are primarily delivered via rapid, non-oral routes (such as inhalation, nasal, or subcutaneous) while preventives include a variety of unrelated treatments such as corticosteroids, verapamil, and galcanezumab. Neuromodulation is becoming an increasingly popular option, both non-invasively such as vagus nerve stimulation when medical treatment is contraindicated or side effects are intolerable, and invasively such as occipital nerve stimulation when medical treatment is ineffective. Clinically, this collection of treatment types provides a range of options for the informed clinician. Scientifically, this collection provides important insights into disease mechanisms., Methods: Two authors performed independent narrative reviews of the literature on guideline recommendations, clinical trials, real-world data, and mechanistic studies., Results: Cluster headache is treated with acute treatments, bridge treatments, and preventive treatments. Common first-line treatments include subcutaneous sumatriptan and high-flow oxygen as acute treatments, corticosteroids (oral or suboccipital injections) as bridge treatments, and verapamil as a preventive treatment. Some newer acute (non-invasive vagus nerve stimulation) and preventive (galcanezumab) treatments have excellent clinical trial data for episodic cluster headache, while other newer treatments (occipital nerve stimulation) have been specifically tested in treatment-refractory chronic cluster headache. Most treatments are suspected to act on the trigeminovascular system, the autonomic system, or the hypothalamus., Conclusions: The first-line treatments have not changed in recent years, but new treatments have provided additional options for patients.

The current study was aimed to investigate the beneficial effect of sumatriptan, a 5-hydroxytryptamine 1B/1D (5HT 1B/1D ) receptor agonist, on gastric ulcer in rats via stimulating 5HT 1B/1D receptors and suppressing pro-inflammatory cytokines. Rats were allocated into three models of gastric ulcer: indomethacin (30 mg/kg, PO), water immersion restraint stress (WRS) and ethanol (5 ml/kg PO). Animals were administered with sumatriptan (0.01, 0.1, 0.3 and 1 mg/kg, i.p) 30 min before gastric ulcer induction. GR-127935 (0.01 mg/kg, i.p, a selective 5HT 1B/1D antagonist) was administered 30 min before sumatriptan (0.1 mg/kg) injection. Macroscopic assessments (J-score), ELISA analysis of tumour necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) and histopathological changes were performed on the rat's stomach tissues. Gastric ulcer induction in three models caused an increase in J-score, TNF-α, IL-1β and microscopic features. Sumatriptan (0.1 mg/kg) significantly improved gastric injury induced by indomethacin, WRS and ethanol through the reduction in the J-score, TNF-α, IL-1β and microscopic lesions. Concurrent administration of GR-127935 (0.01 mg/kg) with sumatriptan (0.1 mg/kg) reversed the gastroprotective effect of sumatriptan in three models. Sumatriptan possessed gastroprotective effects on indomethacin-, WRS- and ethanol-induced gastric damage in rats via the possible involvement of the 5HT 1B/1D receptors., (© 2023 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

Ritlecitinib, an inhibitor of Janus kinase 3 and hepatocellular carcinoma family kinases, is in development as potential treatment for several inflammatory diseases. In vitro studies presented ritlecitinib as an inhibitor of hepatic organic cation transporter (OCT) 1, renal transporters OCT2 and multidrug and toxin extrusion (MATE) proteins 1/2K using multiple substrates, and ritlecitinib's major inactive metabolite M2, as an inhibitor of OCT1. A clinical interaction study with an OCT1 drug probe (sumatriptan) and relevant probe biomarkers for OCT/MATE was conducted to assess the effect of ritlecitinib on these transporters in healthy adult participants. The selectivity of sumatriptan for OCT1 was confirmed through a series of in vitro uptake assays. A simple static model was used to help contextualize the observed changes in sumatriptan area under the plasma concentration-time curve (AUC). Coadministration of a single 400-mg dose of ritlecitinib increased sumatriptan AUC from time 0 to infinity (AUC inf ) by ≈30% relative to a single 25-mg sumatriptan administration alone. When administered 8 hours after a ritlecitinib dose, sumatriptan AUC inf increased by ≈50% relative to sumatriptan given alone. Consistent with OCT1 inhibition, the AUC from time 0 to 24 hours of isobutyryl-L-carnitine decreased by ≈15% after ritlecitinib. Based on the evaluation of the renal clearance of N 1 -methylnicotinamide, ritlecitinib does not exert clinically meaningful inhibition on renal OCT2 or MATE1/2K. This study confirmed that ritlecitinib and M2 are inhibitors of OCT1 but not OCT2 or MATE1/2K in healthy adults., (© 2023 Pfizer Inc. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Sumatriptan is an organic chemical compound from the tryptamine group. It is used as a medicine for migraine attacks and in the treatment of cluster headaches. In this work, a new voltammetric method is proposed for highly sensitive SUM determination, using glassy carbon electrodes modified with carbon black and titanium dioxide suspension. The novelty of the presented work is the usage of the mixture of carbon black and TiO 2 as glassy carbon electrode modifier for the first time for SUM determination. The mentioned sensor was characterized by great repeatability and sensitivity of measurements, which resulted in the obtention of a wide range of linearity and a low detection limit. The electrochemical properties of the CB-TiO 2 /GC sensor was characterized using the LSV and EIS method. The effect of different factors on the SUM peak, such as supporting electrolyte type, preconcentration time and potential, or influence of interferents, were tested using the square wave voltammetry technique. The linear voltammetric response for the analyte was obtained in the concentration range of 5 nmol L -1 to 150 μmol L -1 with a detection limit of 2.9 nmol L -1 for a preconcentration time of 150 s in the 0.1 mol L -1 phosphate buffer pH 6.0. The proposed method was successfully applied for highly sensitive sumatriptan determination in complex matrices, such as tablets, urine, and plasma, with a good recovery parameter (94-105%). The presented CB-TiO 2 /GC electrode is characterized by great stability, it was used for 6 weeks without significant changes in the SUM peak current. Amperometric and voltammetric measurements of SUM under the flow injection conditions were also performed to indicate the possibility of its fast and accurate determination with a time of single analysis of approx. 30 s.

Introduction: Patients are seeking greater involvement in their healthcare. It therefore may be beneficial to provide guidance on initial oral sumatriptan dose selection for the treatment of acute migraine in nontraditional settings, such as telehealth and other remote forms of medical care. We sought to determine whether clinical or demographic factors are predictive of oral sumatriptan dose preference., Methods: This was a post hoc analysis of two clinical studies designed to determine preference for 25, 50, or 100 mg oral sumatriptan. Patients were aged 18-65 years with at least a 1 year history of migraine and experienced, on average, between one and six severe or moderately severe migraine attacks per month, with or without aura. Predictive factors were demographic measures, medical history, and migraine characteristics. Possibly predictive factors were identified using three analyses: classification and regression tree analysis, marginal significance (P < 0.1) within a full-model logistic regression, and/or selection within a forward-selection procedure in a logistic regression. A reduced model containing the variables identified in the preliminary analyses was developed. Due to differences in study design, data were not combined., Results: A dose preference was expressed by 167 patients in Study 1 and 222 patients in Study 2. Gender and medical history of urologic and/or psychological conditions in Study 1 and duration of migraine history, height, and medical history of endocrine or neurologic disease and headache severity in Study 2 were identified as possibly predictive. The predictive model showed low positive predictive value (PPV; 23.8%) and low sensitivity (21.7%) for Study 1. For Study 2, the model showed moderate PPV (60.0%) but low sensitivity (10.9%)., Conclusions: No clinical or demographic characteristics alone or in combination were consistently or strongly associated with preference for oral sumatriptan dose level., Trial Registration: The studies on which this paper is based were conducted before trial registration indexes were introduced., (© 2023. The Author(s).)

Background: Mesenteric ischemia has remained without effective pharmacological management for many years. Sumatriptan, an abortive medication for migraine and cluster headaches, has potent anti-inflammatory properties and ameliorated organ ischemia in previous animal studies. Similarly, inhibition of the kynurenine pathway ameliorated renal and myocardial ischemia/reperfusion (I/R) in many preclinical studies. Herein, we assessed the effect of sumatriptan on experimental mesenteric I/R and investigated whether kynurenine pathway inhibition is a mechanism underlying its action., Methods: Ischemia was induced by ligating the origin of the superior mesenteric artery (SMA) and its anastomosis with the inferior mesenteric artery (IMA) with bulldog clamps for 30 min. Ischemia was followed by 1 h of reperfusion. Sumatriptan (0.1, 0.3, and 1 mg/kg ip) was injected 5 min before the reperfusion phase, 1-methyltryptophan (1-MT) (100 mg/kg iv) was used to inhibit kynurenine production. At the end of the reperfusion phase, samples were collected from the jejunum of rats for H&E staining and molecular assessments., Results: Sumatriptan improved the integrity of intestinal mucosa after I/R, and 0.1 mg/kg was the most effective dose of sumatriptan in this study. Sumatriptan decreased the increased levels of TNF-α, kynurenine, and p-ERK but did not change the decreased levels of NO. Furthermore, sumatriptan significantly increased the decreased ratio of Bcl2/Bax. Similarly, 1-MT significantly decreased TNF-α and kynurenine and protected against mucosal damage., Conclusions: This study demonstrated that sumatriptan has protective effects against mesenteric ischemia and the kynurenine inhibition is potentially involved in this process. Therefore, it can be assumed that sumatriptan has the potential to be repurposed as a treatment for acute mesenteric ischemia., (© 2023. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

Background: Migraine and depression have a bi-directional, positive association. The likelihood of these conditions being comorbidities is high, thus, the possibility of concomitant use of an antidepressant and a triptan is also increased. Case Presentation: We present a case of a 39-year-old female with a history of migraine with aura and depression who had brief episodes of exacerbated depressive symptoms following oral administration of sumatriptan 100 mg daily as needed while taking various selective serotonin reuptake inhibitor (SSRI) and serotonin and norepinephrine reuptake inhibitor (SNRI) medications on different occasions. The patient experienced 30-minute episodes of sweating and subjective increase in temperature approximately 2-3 hours after administration of sumatriptan 100 mg. This was followed by a transient exacerbation of sadness described by the patient as unhappiness, hopelessness, and tearfulness, which lasted 1 to 2 hours. To date, there are no other published case reports that have described this particular presentation. Several studies have reported possible serotonin syndrome as a result of the combination. Current evidence and known pharmacological actions of SSRIs/SNRIs and triptans are not well-defined enough to explain how one can experience episodic worsening depression. Conclusion: This case illustrates that clinicians should consider other potential adverse effects of the combined use of triptans and SSRIs/SNRIs beyond serotonin syndrome.

Background and Purpose: The response to cluster headache treatments has a high interindividual variation. To date, treatment response has only been assessed by a candidate gene approach and no investigations into metabolic pathways have been performed. Our aim was to investigate the association between the polygenetic risk of cluster headache and treatment response to first-line cluster headache treatments as well as known functional variants of CYP3A4 and the response to verapamil. Further, it was aimed to replicate previous single nucleotide polymorphisms found to be associated with treatment response in cluster headache and/or migraine., Methods: In, 508 cluster headache patients diagnosed according to the International Classification of Headache Disorders were genotyped and participated in a semi-structured interview to evaluate treatment response. Polygenetic risk scores were calculated by the effect retrieved from a meta-analysis of the latest two genome-wide association studies on cluster headache., Results: Inferior treatment response to oxygen, triptans and verapamil is associated with chronicity of cluster headache were confirmed but no evidence was found that a response could be predicted by a high genetic risk of cluster headache. Likewise, verapamil response was not associated with functional variants of CYP3A4. No support of the genetic variants previously reported to be associated with treatment response to triptans or verapamil was found., Conclusion: The clinically relevant variation in treatment response for cluster headache was not influenced by genetic factors in the present study., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Sumatriptan (SUM), a serotonin activator used to treat migraines and cluster headaches. Molecular spectroscopic methods including fluorescence quenching, time dependent fluorescence, FRET, absorption, circular dichroism, differential scanning calorimetric and computational approaches were employed to unravel the interaction between sumatriptan and bovine serum albumin (BSA). The fluorescence quenching studies suggested the interaction between SUM and BSA with a moderate binding with the binding constant ( K b ) in the order of 10 4 . The findings of temperature and time dependent fluorescence quenching studies confirmed the role of static quenching mechanism. Thermodynamic parameters suggested the key role of electrostatic force in the interaction of SUM with BSA. Absorption and CD spectral studies revealed the bioenvironmental changes around the Trp in BSA upon binding of SUM. Calorimetric based thermal denaturation results confirmed that the thermal stability of BSA was improved in the presence of SUM. resulted in the this decreased flexibility of protein chain. Site competitive studies indicated SUM was located in the hydrophobic cavity of site I which was further confirmed by the docking and dynamic simulation studies. Additionally, molecular dynamics simulations inferred the microenvironmental condition around the SUM and the amino acids and forces involved in the binding of SUM with BSA.Communicated by Ramaswamy H. Sarma.

The study's goal was to create an in situ intrarectal mucoadhesive gel of sumatriptan (SMT) combining mucoadhesive polymer (xyloglucan) and thermosensitive polymers (poloxamer 407 and poloxamer 188) to prolong rectal residence time for treatment of migraines. Nine SMT mucoadhesive rectal in situ gel (RIG) formulas were created by mixing poloxamer 407 (18%, 19%, or 20%) with poloxamer 188 (5%), a mucoadhesive polymer at various doses (0.1, 0.2, and 0.3) as well as SMT (25 mg/ml). The prepared suppositories underwent for mucoadhesive force, gelation temperature, and gelation time. When SMT and mucoadhesive polymer were added to the poloxamer mixture, the gelation temperature dropped; however, poloxamer 188 had the opposite effect. These polymers supported the prepared liquids' ability to adhere to mucous membranes and form a strong gel. The transition gelation temperature of the poloxamer solution rose as a result of the addition of poloxamer 188. The findings showed that the formula RIG5 which is composed of poloxamer 407 (19%), poloxamer 188 (5%), and xyloglucan (0.2%) had an ideal transition temperature of 36.33°C, gel strength of 44.66°C, mucoadhesive force of 6409°C, and in vitro drug release of 93.98% over an 8-hour period. In light of this, it can be said that SMT was successfully manufactured as RIG without causing any chemical reaction with its additives., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Advanced Pharmaceutical Technology & Research.)

Scientific literature describes that sumatriptan is metabolized by oxidative deamination of its dimethylaminoethyl residue by monoamine oxidase A (MAO A) and not by cytochrome P450 (CYP)-mediated demethylation, as is usual for such structural elements. Using recombinant human enzymes and HPLC-MS analysis, we found that CYP enzymes may also be involved in the metabolism of sumatriptan. The CYP1A2, CYP2C19, and CYP2D6 isoforms converted this drug into N-desmethyl sumatriptan, which was further demethylated to N,N-didesmethyl sumatriptan by CYP1A2 and CYP2D6. Otherwise, sumatriptan and its two desmethyl metabolites were metabolized by recombinant MAO A but not by MAO B to the corresponding acetaldehyde, with sumatriptan being only a poor substrate for MAO A compared to the N-demethylated and the N,N-didemethylated derivatives., (© 2023 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Background: For many years triptans have been the cornerstone of acute migraine treatment. Nevertheless, treatment with triptans may not always be initiated due to contraindications (seen in approximately one fifth of patients) or inadequate response (seen in approximately one third of patients). New acute therapies, including 5-hydroxytryptamine (5-HT) 1F receptor agonists, also known as ditans (lasmiditan) and small molecule antagonists of the calcitonin gene-related peptide receptor, also known as gepants (rimegepant and ubrogepant), may be an effective alternative. Methods: We searched Pubmed for keywords, summarized the literature and provided a comprehensive review on the place of next generation acute migraine specific treatments among triptans. Results and conclusion: Post-hoc analyses reported no differences in efficacy of gepants/ditans between responders and non-responders to triptans, but research is hampered by lack of consensus on the definition of non-responder. Due to (partially) overlapping mechanisms of action, it remains unknown whether combination therapy with lasmiditan, gepants and triptans will have added value over monotherapy. Preclinical studies and post-hoc analyses cautiously indicate that these new drugs are safe for patients with cardiovascular risk factors. However, long-term studies are needed to prove cardiovascular safety. The risk of developing medication overuse headache may differ between triptans, ditans and gepants, but further studies are needed to confirm this difference. Head-to-head randomized controlled trials of acute therapies and combinations of therapies are needed to determine their place in migraine treatment among established therapies.

Naproxen sodium (NAP) and Sumatriptan (SUM) are pharmacological migraine therapies that are more efficient when administered in combination. In the present work, an electrochemical sensor was developed for simultaneous and sensitive NAP and SUM detection using MWCNTs decorated with ZnO, NiO and Fe 3 O 4 nanoparticles on glassy carbon electrode (GCE). This report is the first research on simultaneous electrochemical measuring the target drugs based on the literature. The data show that modification of the GCE surface with ZnO/NiO/Fe 3 O 4 /MWCNTs nanocomposite remarkably improves the electro-oxidation peaks currents but the peaks potential of NAP and SUM have shifted to the lower potential which demonstrates that electro-oxidation of target drugs have done more easier than GCE at the surface of modified electrode. The nanocomposite was recognized by using Fourier transform infrared spectroscopy (FTIR) and field emission scanning electron microscopy (FE-SEM), and X-ray diffraction (XRD). The improved electrode was estimated by various methods, including cyclic voltammetry (CV), square wave voltammetry (SWV), and electrochemical impedance spectroscopy (EIS) techniques. Influencing parameters containing the supporting electrolytes, pH, scan rate, deposition potential, and accumulation time were optimized. The linear detection ranges were from 4.00 nMto 350.00 μM for NAP and from 6.00 nM to 380.00 μM for SUM, with the detection limits of 3.00 nMfor NAP and 2.00 nM for SUM, respectively. The repeatability, linearity, and selectivity of ZnO/NiO/Fe 3 O 4 /MWCNTs/GCE were investigated, and the received outcomes divulged the efficiency of the electrode. The consequence of high-performance liquid chromatography (HPLC) and recovery show the method's suitability for the simultaneous determination of NAP and SUM in the biological fluids and pharmaceutical compounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Early post-stroke seizure frequently occurs in stroke survivors within the first few days and is associated with poor functional outcomes. Therefore, efficient treatments of such complications with less adverse effects are pivotal. In this study, we investigated the possible beneficial effects of lasmiditan and sumatriptan against post-stroke seizures in mice and explored underlying mechanisms in their effects., Methods: Stroke was induced by double ligation of the right common carotid artery in mice. Immediately after the ligation, lasmiditan (0.1 mg/kg, intraperitoneally [i.p.]) or sumatriptan (0.03 mg/kg, i.p.) were administered. Twenty-four hours after the stroke induction, seizure susceptibility was evaluated using the pentylenetetrazole (PTZ)-induced clonic seizure model. In separate experiments, naltrexone (a non-specific opioid receptor antagonist) and glibenclamide (a K ATP channel blocker) were administered 15 min before lasmiditan or sumatriptan injection. To evaluate the underlying signaling pathways, ELISA analysis of inflammatory cytokines (TNF-α and IL-1β) and western blot analysis of anti- and pro-apoptotic markers (Bcl-2 and Bax) were performed on mice isolated brain tissues., Results: Lasmiditan (0.1 mg/kg, i.p.) and sumatriptan (0.03 mg/kg, i.p.) remarkably decreased seizure susceptibility in stroke animals by reducing inflammatory cytokines and neuronal apoptosis. Concurrent administration of naltrexone (10 mg/kg, i.p.) or glibenclamide (0.3 mg/kg, i.p.) with lasmiditan or sumatriptan resulted in a higher neuroprotection against clonic seizures and efficiently reduced the inflammatory and apoptotic markers., Conclusion: Lasmiditan and sumatriptan significantly increased post-stroke seizure thresholds in mice by suppressing inflammatory cytokines and neuronal apoptosis. Lasmiditan and sumatriptan seem to exert higher effects on seizure threshold with concurrent administration of the opioid receptors or K ATP channels modulators., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

In this work, Ni-Co layered double hydroxide (Ni-Co LDH) hollow nanostructures were synthesized and characterized by X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), and Fourier-transform infrared spectroscopy (FT-IR) techniques. A screen-printed electrode (SPE) surface was modified with as-fabricated Ni-Co LDHs to achieve a new sensing platform for determination of sumatriptan. The electrochemical behavior of the Ni-Co LDH-modified SPE (Ni-CO LDH/SPE) for sumatriptan determination was investigated using voltammetric methods. Compared with bare SPE, the presence of Ni-Co LDH was effective in the enhancement of electron transport rate between the electrode and analyte, as well as in the significant reduction of the overpotential of sumatriptan oxidation. Differential pulse voltammetry (DPV) was applied to perform a quantitative analysis of sumatriptan. The linearity range was found to be between 0.01 and 435.0 μM. The limits of detection (LOD) and sensitivity were 0.002 ± 0.0001 μM and 0.1017 ± 0.0001 μA/μM, respectively. In addition, the performance of the Ni-CO LDH/SPE for the determination of sumatriptan in the presence of naproxen was studied. Simultaneous analysis of sumatriptan with naproxen showed well-separated peaks leading to a quick and selective analysis of sumatriptan. Furthermore, the practical applicability of the prepared Ni-CO LDH/SPE sensor was examined in pharmaceutical and biological samples with satisfactory recovery results., Competing Interests: The authors declare no conflict of interest.

Spinal anaesthesia (SA) is a common method during surgery due to easy administration, rapid effects, relaxes muscles and controls pain. But, post-dural puncture headache (PDPH) is a common problem after SA that occurs in 6%-36% of SA. We assessed the effect of four common treatment drugs sumatriptan, theophylline, pregabalin and oral caffeine on prevention of PDPH. In this systematic review, all randomized clinical trials (RCTs) during January 2015 and December 2021 were searched from PubMed, Google Scholar, Web of Science, Cochrane review and Clinical Key with a specific search strategy. The article qualities were assessed by two independent authors and were screened for relevant sources based on inclusion and exclusion criteria. Moreover, the included articles data were extracted and checked for regular basis. A total of 421 articles were identified and 193 articles were removed following a preliminary review and finally, 14 articles were included in review. Overall, we identified five RCTs on the effect of caffeine, two RCTs on the effect of sumatriptan, three RCTs on theophylline, three RCTs on pregabalin and one RCT on theophylline and sumatriptan in PDPH prevention. This review supports the effects of theophylline, pregabalin and sumatriptan in the prevention of PDPH incidence and treatment of PDPH intensity, but we cannot draw the same conclusions about caffeine due to some negative results about the caffeine effect. Nevertheless, this extracted conclusion should be considered and interpreted with caution and limited generalizations due to the small number of studies, the variety of evaluated drugs and measures, the low sample size and the bias presented., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of the West African College of Surgeons.)

Background: We aimed at evaluating adverse drug reactions during the post-marketing phase with erenumab as the suspected/interacting drug in Eudravigilance, with the final goal of investigating the consistency of the disproportionality signals (DS) for erenumab in Eudravigilance and the American Food and Drug Administration Adverse Event Reporting System (FDA FAERS) and undetected DS from Eudravigilance., Research Design and Methods: Eudravigilance was screened in the period from October 2019 to October 2020. Disproportionality measure was performed using the Reporting Odds Ratio (ROR) according to the guidelines by the European Medicine Agency and using sumatriptan as the control group., Results: 3381 cases were reported in the study period. Forty DS were identified both in Eudravigilance and FAERS. Sixteen DS were not identified in FAERS, 10 DS were found to have biological probability and six DS were considered false-positive and potentially related to confounding by indication. The three system organ classes with the highest proportion of adverse events were general disorders and administration site conditions (16.12%), nervous system disorders (15.95%), and gastrointestinal disorders (13.59%)., Conclusions: Adverse events reports were mostly reported as non-serious. Co-analysis of multiple spontaneous reported databases unveiled undetected DS for erenumab in individual databases. Future studies should be conducted to confirm the associations and potential clinical implications.

Competing Interests: Competing interests: None declared.

Sensitive and selective spectrophotometric and spectrofluorimetric methods have been developed for the estimation of two anti-migraine drugs, namely sumatriptan succinate (SUM) and zolmitriptan (ZOL). These methods depend on producing a yellow-coloured product after the reaction of the two drugs with 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD-Cl). The reaction products exhibited maximum absorbance at 481 nm in borate buffer of pH 9 and fluorescence emission peak at 540 nm after excitation at 470 nm for the two drugs. The linear ranges were 5-60 μg/ml for SUM and 5-50 μg/ml for ZOL in the spectrophotometric method (Method I), whereas this was 0.4-4 μg/ml for SUM and 0.5-5 μg/ml for ZOL in the spectrofluorimetric method (Method II). The method validity was assessed according to International Council for Harmonisation (ICH) guidelines. Statistical analysis of the results obtained from the proposed and comparison methods confirmed that the proposed methods were highly accurate and precise. The suggested methods could be used for the determination of the mentioned drugs in both pure form and in tablets., (© 2022 John Wiley & Sons Ltd.)

Sumatriptan succinate and prochlorperazine maleate are a clinically proven combination for treating migraine and associated nausea and vomiting. Classical oral dosage forms are not frequently workable in migraine because of the associated nausea/vomiting, and no effective fixed dose combination is available. Thus, the aim of the study was to optimize a combined sumatriptan-prochlorperazine orodispersible film for rapid release of drugs. Orodispersible films were prepared by solvent casting method using varied amounts of polyvinyl alcohol and glycerol as film former and plasticizer, respectively, along with fixed levels of other ingredients employing central composite design. The optimum film (VF) demonstrated disintegration and total dispersion times as 21 s and 2.3 min, respectively. Tensile strength and Young's modulus were 8.86 ± 0.37 MPa and 24.15 ± 0.07 MPa, respectively. The in vitro T80% of both drugs from the ODF was achieved within 4 min. The film was palatable and disintegrated in 2 min in buccal cavity of human volunteers. Permeation study through goat mucosa demonstrated 100% permeation of both drugs within 15 min. X-Ray diffraction and differential scanning calorimetry supported drugs being amorphous and Fourier transform infrared demonstrated drug-excipient compatibility in optimized film. A judicious combination of sumatriptan succinate and prochlorperazine maleate could be prepared in orodispersible films for the possible relief of migraine., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Transcranial Doppler ultrasonography is used to study intracranial blood flow changes associated with migraine in humans, but whether this method is helpful in preclinical settings is yet unknown. To identify changes in rat intracranial blood flow specific to trigeminovascular activation-a key process in migraine pathophysiology-we measured Doppler indices in the middle cerebral artery and basilar artery before, during, and after dural or somatosensory electrical stimulation. Hemodynamic changes specific to dural stimulation were tested further in separate experiments. After baseline recordings, the animals received cumulative infusions of valproate (100 mg/kg, trice), sumatriptan (0.3, 1, and 3 mg/kg), or saline, and dural stimulation with measurement of Doppler indices was repeated every 10 min for 1 h. Several parameters of blood flow in the rat middle cerebral artery underwent alterations specific to trigeminovascular activation. These changes, however, were insensitive to valproate and sumatriptan and diminished over time. These findings question the reliability of blood flow velocity variations in large intracranial vessels as biological markers of migraine-related processes and do not support the idea of using transcranial Doppler ultrasonography for preclinical screening of antimigraine treatments, at least in the model of acute trigeminovascular activation in rats.

Drug information can be obtained from various drug information sources that were available as government (National Formulary of India [NFI]; Central Drugs Standard Control Organization [CDSCO]), as well as commercial documents (Current Index of Medical Specialties [CIMS] and Monthly Index of Medical Specialties [MIMS]). Irrational drug usage may happen due to wide variation in the information available in these sources. In this study, we tried to assess these variations in a sample of drugs for the acute-specific management of migraine with ergot and Triptans antimigraine drugs in drug information sources such as NFI, CIMS, MIMS, and CDSCO. Scoring was done for various drug information based on the completeness of information about drugs used in acute-specific management of migraine. The scores for the completeness of drug information about the selected antimigraine drugs are 18.37% for CIMS (Ergotamine, Sumatriptan, Rizatriptan, and Zolmitriptan), 21.1% for NFI (Dihydroergotamine, Sumatriptan), 72.79% for MIMS (Ergotamine tartrate, Sumatriptan, Rizatriptan, Naratriptan, zolmitriptan, Almotriptan) and 21.77% for CDSCO (Ergotamine tartrate, Sumatriptan, Rizatriptan, Naratriptan, Zolmitriptan, eletriptan and almotriptan). The information for the antimigraine drugs available from various sources found to so much deficient. Necessary steps need to be taken in case of government public or hard documents to streamline drug information available with them as well the commercial documents as to provide reliable drug information uniformly for promoting rational use of the drug., Competing Interests: None

Aim: To evaluate pharmacokinetic interactions of atogepant with sumatriptan, an open-label, randomized, crossover study was conducted. Patients & methods: Thirty healthy adults received atogepant 60 mg, sumatriptan 100 mg, or coadministered drugs. Primary end point was geometric mean ratios (GMRs) and 90% CIs of interventions for area under the plasma concentration-time curve from time 0 to t (AUC 0-t ) or infinity (AUC 0-∞ ) and peak plasma concentration (C max ). Results: Atogepant GMRs for AUC 0-t and AUC 0-∞ versus with sumatriptan were within 90% CI 0.80-1.25, indicating no interaction; atogepant C max was reduced by 22% (GMR: 0.78; 90% CI: 0.69-0.89) with sumatriptan. Sumatriptan GMRs for AUC 0-t , AUC 0-∞ and C max versus with atogepant were within 90% CI 0.80-1.25. Conclusion: Atogepant with sumatriptan had no clinically relevant pharmacokinetic interactions.

Mucosal inflammation in colitis is associated with changes in the intestinal serotonin (5-HT) level. Sumatriptan, a 5-HT 1B/1D receptor agonist, has demonstrated anti-inflammatory characteristics. The purpose of this study was to determine the effects of sumatriptan in a rat model of acute experimental colitis and to elucidate the probable participation of presynaptic 5-HT 1B/1D receptors. To induce colitis, acetic acid (4%) was injected intrarectally. Treatments were given intraperitoneally (IP) once daily over 3 consecutive days starting 1-h post-induction. Sumatriptan was given at 0.5, 1, 2, and 5 mg/kg. GR-127935, a 5-HT 1B/1D receptor antagonist, was injected (0.1 and 0.3 mg/kg) 30 min prior to the most effective dose of sumatriptan (1 mg/kg). On day 4, the colon samples were isolated. Significant enhancements of the tissue tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), microscopic and macroscopic damages, body weight losses, and also reductions in tissue superoxide dismutase (SOD) and 5-HT were observed in colitis rats. On the other hand, sumatriptan at doses 0.5, 1, and 2 mg/kg could diminish pathologic changes in the measured biomarkers, histopathologic damages, and body weight losses. Although GR-127935 at dose 0.3 mg/kg could markedly improve the pathologic indexes, its sub-effective dose (0.1 mg/kg) reversed the protective effect of sumatriptan (1 mg/kg). Moreover, sumatriptan (1 and 5 mg/kg) and GR-127935 (0.3 mg/kg) increased the serotonin level. Post-treatment with low-dose sumatriptan demonstrated a protective impact on this peripheral inflammatory condition. Notably, this protective effect may be mediated, at least in part, through 5-HT 1B/1D receptors, as well as anti-inflammatory and anti-oxidative characteristics., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Migraine headaches can cause severe pain for patients and lead them to multiple visits to the emergency department (ED). This study aimed to evaluate the efficacy of propofol + sumatriptan combination in comparison with sumatriptan alone in the management of acute migraine headaches., Methods: This triple-blind clinical trial involved patients who referred to two emergency departments with acute migraine headaches. Patients were randomly assigned to control (sumatriptan and placebo) or intervention (propofol and sumatriptan) groups for comparison of the efficacy and side effects of treatment., Results: In this study, 60 patients were included whose mean age was 31±8.8 years, and headaches were more common among women. After 30 and 60 minutes from the beginning of treatment, the mean pain score reduction in the intervention group was significantly greater than that in the control group (p=0.012, p=0.024). In addition, the rate of chest tightness in the control group was significantly higher than the intervention group. The absolute risk reduction of adverse events (Chest tightness, Bradycardia, hypotension, and etc.), in patients with acute migraine headache taking propofol and sumatriptan treatment, was 32.18% (95% CI: 8.02 - 56.35)., Conclusions: This study supports the use of propofol for treatment of acute migraine headaches and shows that combining sumatriptan with propofol is more effective in relieving migraine headaches and the associated symptoms than using sumatriptan alone. However, more studies with longer follow-ups are still needed., Competing Interests: All authors confirm thet there is not any financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work.

Seizure occurs as a result of uncontrolled electrical disturbances within the brain. Various biomolecules such as N-methyl-D-aspartate (NMDA), nitric oxide (NO), and cAMP response element-binding protein (CREB) have been implicated in the pathophysiology of seizure. Sumatriptan is a specific 5-Hydroxytryptamine 1B/1D receptor agonist and has neuroprotective effects in various neuropsychiatric disorders. In the current study, we tried to investigate the possible interaction of sumatriptan with NMDA/NO and CREB signaling pathway in PTZ induced seizure. For this purpose, various agonist and antagonist of NMDA such as MK-801 and Ketamine, NO precursor L-ARG, and NOS inhibitors L-NAME and 7-NI were co-administered with sumatriptan in PTZ induced seizure model. The level of nitrite in mice hippocampus was determined by Griess reaction. The gene expression of NR1, NR2A, NR2B, and CREB were quantified by quantitative real time-polymerase chain reaction (qRT-PCR). Furthermore, the involved neuronal nitric oxide synthase (nNOS) protein expression was examined via western blot analysis. Effective dose of sumatriptan (1.2 mg/kg) alone and subeffective dose of sumatriptan (0.3 mg/kg) in combination with NMDA and/or NO antagonist showed significant (P < 0.001) anticonvulsant activity in mice. Furthermore, sumatriptan significantly inhibited the PTZ-induced mRNA expression of NR2A (P < 0.0001), NR2B (P < 0.05), and CREB (P < 0.01). Also, the expression of nNOS protein in PTZ treated group was reversed by sumatriptan (P < 0.01). Hence, current findings suggest that the anticonvulsant effect of sumatriptan was due to down regulation of NMDA/NO and CREB signaling pathway., (© 2021 Société Française de Pharmacologie et de Thérapeutique.)