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BACKGROUND Monocarboxylate transporter 8 (MCT8) is the first thyroid hormone transporter that has been linked to a human disease. Besides genetic alterations other factors might impair MCT8 activity. AIM This study aimed at investigating whether some common drugs having a structural similarity with TH and/or whose treatment is associated with thyroid function test abnormalities, or which behave as antagonists of TH action can inhibit MCT8-mediated T3 transport. METHODS [125I]T3 uptake and efflux were measured in COS-7 cells transiently transfected with hMCT8 before and after exposure to increasing concentrations of hydrocortisone, dexamethasone, prednisone, prednisolone, amiodarone, desethylamiodarone, dronedarone, buspirone, carbamazepine, valproic acid, and L-carnitine. The mode of inhibition was also determined. RESULTS Dexamethasone significantly inhibited T3 uptake at 10 μM; hydrocortisone reduced T3 uptake only at high concentrations, i.e. at 500 and 1000 μM; prednisone and prednisolone were devoid of inhibitory potential. Amiodarone caused a reduction of T3 uptake by MCT8 only at the highest concentrations used (44% at 50 μM and 68% at 100 μM), and this effect was weaker than that produced by desethylamiodarone and dronedarone; buspirone resulted a potent inhibitor, reducing T3 uptake at 0.1-10 μM. L-Carnitine inhibited T3 uptake only at 500 mM and 1 M. Kinetic experiments revealed a noncompetitive mode of inhibition for all compounds. All drugs inhibiting T3 uptake did not affect T3 release. CONCLUSION This study shows a novel effect of some common drugs, which is inhibition of T3 transport mediated by MCT8. Specifically, dexamethasone, buspirone, desethylamiodarone, and dronedarone behave as potent inhibitors of MCT8.

Medications are available to manage alcohol and drug withdrawal, but they are underutilized. Only a handful, such as methadone, buprenorphine, clonidine, or benzodiazepines (chlordiazepoxide, lorazepam, or diazepam), are prescribed. Our objective was to provide an adjusted, inclusive, critical review of the clinical benefits of medications studied for the management of psychoactive substance withdrawal syndrome. We performed an electronic literature search for randomized controlled trials (RCTs) and systematic reviews of RCTs with or without meta-analysis by free-text searching for pharmacotherapy on drug and alcohol withdrawal in eight databases. Doxepin, citalopram, doxepin, and pregabalin manage dysphoria and anxiety during opioid withdrawal. Gabapentin and atenolol lessen alcohol cravings. Gabapentin improves the sleep difficulties associated with cannabis withdrawal. Melatonin reduces anxiety, irritability, depressed mood, and cravings for nicotine. Doxepin alleviates benzodiazepine withdrawal anxiety and depression. Riluzole reduces amphetamine craving and depression. Modafinil reduces the intensity of cocaine cravings. Controlled trials on caffeine withdrawal were lacking. Buspirone and gabapentin accounted for more than 70% of all the medications studied. No conclusions can be drawn on adverse events because of reporting inconsistencies in the studies reviewed. Substitution therapy seems to be the foremost choice for the treatment of psychoactive substance withdrawal. However, other medications are available but poorly utilized. Practitioners can use the armory of other available medications to manage psychoactive substance withdrawal. Patients can broaden their medication choice. Voltage-gated ion channels are a promising niche to explore.

Objective: Buspirone, is a medication primarily used for generalized anxiety disorder (GAD), relieve symptoms of anxiety and unipolar depression. This drug exhibit low bioavailability (approximately 5%) due to extensive first-pass metabolism and non-targeted delivery results in numerous side effects. It is taken by mouth, and it may take up to four weeks to have an effect. The present investigation aimed at the development of buspirone in situ nanoemulsion gel to evaluate its potential for efficacious nose to brain drug delivery. Methods: Buspirone-loaded nanoemulsions (BNEs) were prepared by aqueous titration (Spontaneous emulsification) method using Oleic acid, Tween 80, and PEG 400 as oil, surfactant and cosurfactant respectively. The NEs (FC1-FC8) were characterized for pharmaceutical characteristics (Appearance, thermodynamic stability, polydispersity index (PDI) value, globule size, pH, Viscosity, Conductivity and Refractive index). In vitro drug release study from nanoemulsions (NEs) was carried out using Keshary–Chien cell (KC cell, 25 ml) in phosphate buffer pH 5.5. Results: Formulation FC5 with mean globule size of 105.4±1.10 nm, PDI value 0.230±0.01 and drug release 90±0.39% in 6 h (h) was developed as mucoadhesive nanoemulsion gel formulation with 17.5 % W/W of Pluronic F127. The nanoemulsion gel was homogenous, transparent, and possessed a bioadhesive strength of 1605 Dyne/cm2. In vitro cumulative drug release was found to be 90.00±0.39 % at the end of 6 h. Conclusion: The gel had no effect on the structural integrity of nasal mucosa. Hence, the study postulates that In situ nanoemulsion gel of buspirone could be used as an intranasal formulation for targeted brain delivery via nasal route.

Serotonin discontinuation syndrome (SDS) can result in a constellation of symptoms exhibited by infants exposed to selective serotonin reuptake inhibitors or other psychotropic drugs during pregnancy. Currently, there is no consensus regarding the pharmacologic management of SDS. We report our experience with clonidine for the management of a term infant with poor neonatal adaption. The infant exhibited biphasic symptoms of acute toxicity at birth and a plateauing of symptoms, followed by subsequent withdrawal symptomatology requiring the use of clonidine in doses up to 4 mcg/kg/dose every 3 hours for control of symptoms. The 38-week gestation Caucasian male infant was born to a mother with major depressive disorder, which was managed with sertraline, trazodone, venlafaxine, and buspirone throughout her pregnancy. The infant exhibited severe hypertonia at delivery and continued to have hypertonia, tremors, hypoglycemia, and feeding issues upon admission to the NICU. The initial Modified Finnegan Neonatal Abstinence scores were extremely elevated, and clonidine was started at 1 mcg/kg/dose every 3 hours and then the dose was titrated up to 4 mcg/kg/dose. This is the first report documenting the use of clonidine to manage serotonin toxicity at birth followed by subsequent neonatal withdrawal associated with maternal antidepressant drug use during pregnancy.

Background Rett syndrome (RTT) is a severe genetic neurodevelopmental disorder. Emotional, Behavioural and Autonomic Dysregulation (EBAD), is frequent in RTT and is associated with multiple impairments. There are major challenges in the clinical assessment of emotions, behaviours, and autonomic function in RTT patients that limit the management of symptoms. Methods Web-based technology (HealthTracker™) to measure the phenotype, and non-invasive, wearable sensor technology to evaluate autonomic function through Electrodermal Activity (EDA) and Heart Rate Variability (HRV) in 10 RTT patients was used, and treatment response of EBAD symptoms was monitored after different pharmacological treatments. Results and discussion: 4 patients received buspirone, 2 sertraline, 1 gabapentin and 3 were not started on medications. Buspirone normalized the EDA in 3 patients with associated improvement in EBAD, whilst another patient only improved marginally. Both patients treated with sertraline (including one with normal EDA) significantly improved symptomatically. The patients on unchanged regimens showed no change in symptoms and autonomic function. Within 24 h of our assessment, one patient required intensive inpatient care due to septicaemia – this patient had been on gabapentin and showed a sharp and sustained EDA increase without obvious worsening of emotional and behavioural symptoms. Unlike the EDA, the analyses of HRV metrics did not reveal patterns that were associated with clinical outcomes. Our findings suggest a reasonable association of EDA normalization and symptomatic improvement in RTT subjects with EBAD treated with buspirone and point out its potential application as a measure of dysautonomia in RTT. Very high and sustained EDA levels may be a biomarker for concurrent serious physical illness in RTT.

Previously, we have shown that the administration of a selective serotonin reuptake inhibitor fluoxetine or a 5-HT1A receptor agonist buspirone to stressed rats during gestation causes in the offspring alleviation of formalin-induced pain, strengthened by prenatal stress. We have also found that neonatal inflammatory pain strengthens formalin-induced pain in prenatally unstressed rats in later life. In the present study, we investigated the effect of neonatal inflammatory pain on the time-course of the biphasic pain response in the formalin test in prenatally stressed adolescent rats of both sexes to evaluate whether neonatal pain affects the antinociceptive properties of these drugs administered to their depressed mothers during gestation. Our findings demonstrate that neonatal pain modulates in prenatally stressed rats the antinociceptive effect of fluoxetine and buspirone depending on the level of organization of pain response in the central nervous system, the phase of the time-course of the formalin-induced pain, and sex of the rat.

Objective Reports on the pharmacologic treatment of anxiety, including generalized anxiety disorder (GAD), in individuals with Down syndrome (DS) are lacking. Methods We present the case histories of 1 adolescent and 2 young adults with DS and the treatment course of comorbid GAD with buspirone. Results Treatment with buspirone was safe and well-tolerated and resulted in sustained improvement in symptoms of anxiety for a minimum of 2 years in all 3 cases. Conclusion Buspirone's generally benign adverse effect profile makes it well suited for treating anxiety in individuals with DS in light of their common medical comorbidities.

OBJECTIVES Given the rising prevalence of psychiatric symptomatology among college students, this analysis aims to identify temporal trends in psychiatric medication usage. METHODS This analysis used data from the Healthy Minds Study Survey administered between 2007 and 2019, yielding a sample of 320,817 university students. Survey data were examined via descriptive analyses. RESULTS Over the last decade from 2007 to 2018-2019, there was an increase in use of nearly all classes of psychiatric medications, with reported antidepressant medication (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], etc.) use increasing from 8.0% to 15.3%, anti-anxiety medication (benzodiazepines, buspirone, etc.) from 3.0% to 7.6%, psychostimulants from 2.1% to 6.3%, antipsychotics from 0.38% to 0.92%, and mood stabilizers from 0.8% to 2.0% (all p

Gut microbiota regulate the neurodevelopmental processes and brain functions through the regulation of the microbiota–gut interaction and gut–brain communication. Buspirone, an agonist for serotonin 5-HT1A receptors, is used for the treatment of anxiety/depression. Therefore, to understand the gut microbiota-mediated mechanism of buspirone on anxiety/depression, we examined its effect on the immobilization stress (IS) or Escherichia coli K1 (EC)-induced anxiety/depression in mice. Oral or intraperitoneal administration of buspirone significantly suppressed stressor-induced anxiety/depression-like behaviors in the elevated plus maze, light/dark transition, tail suspension, and forced swimming tasks. Their treatments also reduced TNF-α expression and NF-κB+/Iba1+ cell population in the hippocampus and myeloperoxidase activity and NF-κB+/CD11c+ cell population in the colon. Buspirone treatments partially restored IS- or EC-induced gut microbiota perturbation such as β-diversity to those of normal control mice: they reduced the IS- or EC-induced gut Proteobacteria population. In particular, the anxiolytic activity of buspirone was positively correlated with the populations of Bacteroides and PAC001066_g in EC- or IS-exposed mice, while the populations of Lachnospiraceae, KE159660_g, LLKB_g, Helicobacter, and PAC001228_g were negatively correlated. The anti-depressant effect of buspirone was positively correlated with the Roseburia population. The fecal microbiota transplantations from buspirone-treated mice with IS-induced anxiety/depression or normal control mice suppressed IS-induced anxiety/depression-like behaviors and reduced hippocampal NF-κB+/Iba1+ and colonic NF-κB+/CD11c+ cell populations in the transplanted mice. Furthermore, they modified IS-induced perturbation of gut microbiota composition, particularly Proteobacteria, in the transplanted mice. In conclusion, buspirone alleviates IS as well as EC-induced anxiety/depression and colitis. It also suppresses associated neuroinflammation and modulates gut microbiota. Future studies can help to explain the relationship, if any, in the central and peripheral effects of buspirone.

OBJECTIVE The aim of the study was to describe the efficacy of buspirone in controlling nonpharmacological awake and sleep bruxism. METHODS Four cases of nonpharmacological awake and sleep bruxism, one of them with a 20-year-long history, in which buspirone succeeded to control bruxism, are described and discussed. RESULTS Two of the 4 cases had sleep bruxism, and the other 2 cases had sleep and awake bruxism. Besides anxiety, no other predisposing condition was identified. Buspirone was effective in reducing bruxism symptoms in the 4 cases. Mean percentage of bruxism reduction after buspirone was ranked as 65% by subjects. CONCLUSIONS In this small series of cases, buspirone proved effective in the control of nonpharmacological awake and sleep bruxism.

Study design Retrospective analysis of treated inpatients compared to expected neurorecovery from a propensity score-matched national database cohort. Objective Evaluate the effectiveness of buspirone on clinical neurorecovery following traumatic SCI when started during acute inpatient rehabilitation. Setting University-based hospital in Boston, USA. Methods Chart review yielded thirty-one individuals with acute, traumatic SCI treated with buspirone during inpatient rehabilitation from 2011-2017. Propensity score matching to a cohort of individuals from the spinal cord injury model systems (SCIMS) national database was completed. Changes in upper extremity motor score (UEMS), lower extremity motor score (LEMS), American Spinal Injury Association Impairment Scale (AIS), neurological level of injury (NLI), and functional impairment measure (FIM) from admission to discharge and discharge to 1 year were computed and compared between matched pairs (buspirone and mean national SCIMs cohort). A local control cohort not treated with buspirone was similarly compared to a matched mean national SCIMs group to identify location-specific effects. Results From admission to discharge from inpatient rehabilitation, 95% confidence intervals of changes in UEMS (-2.43 to +2.78), LEMS (-1.02 to +6.02), AIS (-0.04 to +0.35), NLI (-0.42 to +1.08), and FIM (-4.42 to +6.40) were not significantly different between those individuals who received buspirone and their propensity-matched SCIMS cohort. Similarly, changes in these metrics were not significantly different at 1-year follow up. Buspirone group individuals with initial clinically complete SCI demonstrated a higher 1-year conversion rate to incomplete injury (6 out of 14; 42.9%) compared to the matched national SCIMS cohort (14 out of 70; 21.2%, p = 0.047) though this was not significantly different from non-buspirone local controls (p = 0.25). Conclusions Retrospective analysis shows no statistically significant difference in gross markers of neurorecovery following acute traumatic SCI when buspirone is initiated indiscriminately during acute inpatient rehabilitation. In individuals with clinically complete SCI, findings suggest possible increased rates of 1-year conversion to incomplete injury.

Objective: The aim of the study was to prepare and evaluate buccal-adhesive tablets of buspirone hydrochloric acid (HCl) that avoids gastric degradation and first-pass metabolism, thereby increasing the drug bioavailability and onset of action. Buspirone HCl belongs to a class anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Methods: In the present work, different ratios of Gantrez MS 955 along with Carbopol 934 were studied to give bioadhesive strength. A 32 full factorial design was applied to investigate the combined effect of Gantrez MS 955 concentration (X1) and Carbopol 934 concentration (X2). Results: Results of the multiple regression analysis revealed that the independent variables significantly affected the dependent variables (bioadhesive strength [Y1], Q2 [Y2], Q3 [Y3], Q4 [Y4]). On the basis of multiple linear regression analysis and contour plot evaluation, it was found that the combination of two polymers possessed excellent mucoadhesive properties allowing ease of application and removal of the tablets from the buccal mucosa. Conclusion: The formulation batch A9 fulfilled all the criteria set from the desirability search. From the in vitro diffusion study, flux was calculated for the optimized batch. A study of the effect of tablet diameter and the environmental factors on the bioadhesion of the tablet was done. To study the environmental factor on bioadhesion, prehydration time and contact time were considered. Results found that increase in prehydration time decrease in bioadhesive strength and increase in contact time increased bioadhesive strength. Thus, a stable buccoadhesive formulation optimized for formulation ingredients and process parameters was prepared successfully.

Stress during critical periods of development can have an abnormal effect on the development of the hypothalamic-pituitary-adrenocortical system (HPA axis), morphogenetic and neurochemical processes of the brain, increasing the risk of psychopathologies. Along with this, there is an increasing number of works indicating the possible adaptive influence of stress. This issue is of practical value which explains the popularity of studies in the mechanisms by which stress at an early age increases the body’s resistance to stress. The available data suggest an important contribution of the serotonergic system to individual differences in the susceptibility to stress events further in life. The balance between the HPA axis and serotonergic system during development is one of the main conditions for the normal functioning of the stress system. We were the first to use pain stress to study the mechanisms of stress neutralization by another pain stress. Previously, we showed an increase in inflammatory pain response in prenatally stressed adult male and female rats. The aim of this work was to investigate the effect of stress during the prepubertal period of development on inflammatory pain, anxiety / depression disorders, and stress reactivity of the HPA axis in prenatally stressed adult male and female rats. In addition, we studied the question of whether prepubertal stress may change the effect of the 5-HT1A receptor agonist buspirone and the serotonin reuptake inhibitor fluoxetine administered to depressed rats during pregnancy on behavioral and hormonal responses in the adult prenatally stressed offspring.

Buspirone, a partial agonist of the 5-HT1aR, due to potential antinociceptive properties can be useful for abdominal pain treatment in IBS patients. Pain-related effects of buspirone can be mediated by the 5-HT1aRs, located within the nucleus tractus solitarius. The 5-HT1aR involvement in pain transmission within the NTS is unclear. The objective of our study was to evaluate the involvement of the 5-HT1aR in abdominal pain transmission within the NTS. Using a model of abdominal pain on urethane-anesthetized rats, two types of NTS pain-related neurons responding to the noxious colorectal distension (CRD) with excitatory and inhibitory sustained patterns of evoked activity were revealed. Buspirone (1.0–4.0 mg kg−1, iv) has complex time- and dose-depended action on the CRD-induced NTS neuron responses. Buspirone inhibits the responses of the excitatory neurons and inverts the responses of the inhibitory pain-related neurons but at a dose of 4.0 buspirone, the effect on NTS pain-related neurons attenuates. The inhibitory effect of buspirone on the CRD-evoked responses of the excitatory NTS neurons is completely blocked by an intra-cerebroventricular administration of buspirone agonist WAY100,635. The inhibitory responses do not change by this agonist. The inhibitory action of buspirone is mediated by supraspinal 5-HT1a receptors however, its excitatory effect on inhibitory neurons does not dependents on these receptors. We proposed that the NTS pain-related neurons could be involved in anti- or pronociceptive effects of buspirone on abdominal pain.

Introduction In Parkinson's disease (PD), anxiety is common, associated with lower health-related quality of life, and undertreated. The primary objective of this study was to determine the tolerability of buspirone for the treatment of anxiety in PD. Methods Individuals with PD and clinically significant anxiety were randomized 4:1 to flexible dosage buspirone or placebo for 12 weeks. Treatment was initiated at 7.5 mg twice daily and titrated based on response and tolerability to an optimal dosage (maximum 30 mg twice daily). The primary outcome was the proportion of participants who failed to complete the study on study drug. Secondary outcomes included adverse events, dosage reductions, motor function, dyskinesias, and anxiety. Results A total of 21 participants enrolled, 4 were randomized to placebo and 17 to buspirone (mean (SD) age 65.5 (9.8), 76.5% male, 88% on concomitant antidepressant or anxiolytic). In the buspirone group, 7 (41%) failed to complete the study on drug, 5 due to intolerability. The median buspirone dosage was 7.5 mg twice daily. No serious adverse events occurred. A total of 9 (53%) buspirone participants experienced adverse events consistent with worsened motor function. In the buspirone group, mean (SD) improvement from baseline to week 12 in Hamilton Anxiety Rating Scale was −3.9 (3.8) and Parkinson Anxiety Scale −7.1 (6.4). Conclusion Tolerability concerns do not support moving immediately forward with a large-scale efficacy trial. However, concomitant anxiolytics may have affected tolerability and a signal of efficacy was seen suggesting that future studies of buspirone monotherapy be considered.

Anxiety disorders have high prevalence and generate major disability. But they have poor treatment targeting because psychiatry lacks diagnostic biomarkers. Right frontal goal-conflict-specific-rhythmicity (GCSR) in the simple stop signal task appears homologous to hippocampal "theta" as an anxiety-process biomarker but is weak and transient. An anticipatory response inhibition task (ARIT) elicits strong subjective conflict and so might generate stronger GCSR. Healthy participants provided EEG during an ARIT, which allowed direct comparison of selective (left, SG; right, GS), and nonselective (both, SS) handed stopping. We assessed GCSR as intermediate versus the average of short and long delay stop-specific power. SG produced right frontal 5-12 Hz GCSR that, as in the SST: significantly correlated with trait anxiety and neuroticism; and was sensitive to pregabalin (75 mg), buspirone (10 mg), and perhaps triazolam (0.25 mg). GS and SS produced faster stopping and only 9-10Hz GCSR, which did not correlate significantly with trait anxiety or neuroticism and was sensitive to pregabalin and buspirone but not triazolam. Source localization suggested that GCSR, like stopping, involves multiple right frontal circuits that depend on response speed. Anxiolytic-sensitive GCSR generalizes from the speeded stop signal task to fixed-time anticipatory response inhibition tasks. GCSR, and the circuits engaged, vary with stop signal RTs conditions. Tasks with longer stop times may be optimal to generate GCSR homologous with rodent hippocampal theta as (a) the first direct anchor of a specific neural form of trait anxiety; (b) a single-dose screen in normal humans for novel anxiolytics; and (c) a potential clinical anxiety biomarker. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

We report here studies of the long-term effects of combined stress in the prenatal and prepubertal periods of development on measures of tonic inflammatory pain in the formalin test and the severity of depression-like behavior, and also the stress reactivity of the hormonal response in adult rats. In addition, the effects of the serotonin (5-HT) reuptake inhibitor fluoxetine and the 5-HT1A receptor agonist buspirone, given chronically to stressed mothers during pregnancy, on various types of adaptive behavior impaired by prenatal stress were assessed in rats of both sexes. The results showed that in rats of both sexes prenatal stress increased the pain response organized at the spinal and supraspinal levels of the central nervous system and that fluoxetine and buspirone normalized responses. Stress during the prepuberal period of development eliminated the effects of prenatal stress on the inflammatory pain responses integrated at the supraspinal level in adult rats; in these conditions, fluoxetine and buspirone had no effects, in contrast to their antinociceptive actions on the pain response integrated at the spinal level. Stress at prepubertal age eliminated sex-related differences seen in depression-like behavior in prenatally unstressed and prenatally stressed rats given physiological saline. Control adult females and adult females exposed to prenatal stress in the prepubertal period showed increases in the plasma corticosterone level after forced swimming as compared with the basal hormone level, though there were no significant differences in the level of stress reactivity of the hormonal response after forced swimming. Thus, the conditions for stress actions increasing stress resistance in adult rats were identified. Stress in the critical period of development formed a phenotype with increased stress resistance to inflammatory pain, which was seen in responses organized at the supraspinal level in adult individuals.

Autism is a complex spectrum of disorders characterized by core behavioral deficits in social communicative behavior, which are also required for comprehensive analysis of preclinical mouse models. As animal models of the core behavioral deficits in autism, two inbred mouse strains, BTBR T+ Itpr3tf/J (BTBR) and BALB/cJ (BALB), were compared with the standard social strain, C57BL/6J (B6), regarding a variety of behavioral factors underlying social communicative interactions, including olfactory and tactile sensory processes, social recognition abilities and behavioral expression strategies. Although both female BTBR and BALB mice can express social recognition and approach behavior depending on the stimuli they encounter, the available sensory modalities, along with modulation of the serotonergic system, differ between the two strains. BALB mice have deficits in using volatile olfactory cues and tactile information in a social context; they fail to exhibit a social approach to volatile cues and seek nonvolatile cues by exhibiting substantial sniff/contact behavior when allowed direct contact with social opponents. Systemic injection of the serotonin (5-HT1A) agonist buspirone has little effect on these social deficits, suggesting a congenitally degraded serotonergic system in BALB mice. In contrast, BTBR mice exhibit impaired body coordination and social motivation-modified olfactory signals, which are relevant to a reduced social approach. A systemic injection of the 5-HT1A agonist restored these social deficits in BTBR mice, indicating that a downregulated serotonergic system is involved in the social deficits exhibited by BTBR mice.

Electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats has been shown to elicit panic-like behaviour and can be a useful as an unconditioned stimulus for modelling anticipatory fear and agoraphobia in a contextual fear conditioning paradigm. In this study, we further analysed our previous data on the effects of escitalopram (a selective serotonin reuptake inhibitor, SSRI) and buspirone (a 5-HT1A receptor partial agonist) on dlPAG-induced anticipatory fear behaviour in a rat model using freezing as a measure. We then attempted to unravel some of the interactions with dopamine signalling using tyrosine hydroxylase (TH) immunohistochemistry to probe the effects on dopaminergic neurons. We showed that acute treatment of escitalopram, but not buspirone, was effective in reducing anticipatory freezing behaviour, while chronic administrations of both drugs were effective. We found that the dlPAG stimulation induced increase number of dopaminergic neurons in the ventral tegmental area (VTA) which was reversed in both chronic buspirone and escitalopram groups. We further found a strong positive correlation between the number of dopaminergic neurons and freezing in the VTA and showed positive correlations between dopaminergic neurons in the VTA and substantia nigra pars compacta (SNpc) in escitalopram and buspirone groups, respectively. Overall, we showed that chronic treatment with an SSRI and a 5-HT1A agonist reduced anticipatory freezing behaviour which seems to be associated, through correlative studies, with a reversal of dlPAG stimulation induced increase in number of dopaminergic neurons in the VTA and/or SNpc.

Objective This study investigated the treatment response and cognitive enhancement effects of buspirone augmentation of escitalopram in patients with major depressive disorder (MDD), according to atypical feature subtypes of MDD.Methods An 8 week, randomized, parallel-controlled, open-label study was conducted. The Columbia Atypical Depression Diagnostic Scale was administered to evaluate atypical features. Patients were assigned randomly to the buspirone augmentation or non-buspirone groups. Symptom severity and cognitive function were evaluated using the 17-item Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Beck Depression Inventory, Beck Anxiety Inventory, digit span test, word fluency test, and Trail Making Tests A and B.Results A total of 89 patients were recruited. There were no significant differences in the measures between the groups; however, among the MDD patients without atypical features, the digit span and word fluency tests were improved by treatment. In the MDD patients without atypical features, the buspirone augmentation group showed a significant improvement on the digit span test compared to the non-buspirone group.Conclusion Buspirone augmentation did not demonstrate significant benefits in MDD patients; however, buspirone augmentation showed greater efficacy for the improvement of cognitive function in MDD patients without atypical features. Our study suggests that atypical features are an important factor for cognitive enhancement in buspirone augmentation treatment in patients with MDD.

Objective In this study, we aimed to investigate the potential interaction of apatinib and buspirone and underlying mechanism. Methods UPLC-MS/MS assay was applied to determine the concentrations of buspirone and its main metabolites (1-PP and 6-OH buspirone) after incubated with liver microsomes. Moreover, the connection of in vitro and in vivo was further determined. Sprague Dawley rats were randomly divided into two groups: group A (20 mg/kg buspirone) and group B (buspirone vs 40 mg/kg apatinib). Tail vein blood was collected and subjected to the UPLC-MS/MS detection. Key findings Apatinib inhibited the generations of 1-PP and 6-OH buspirone dose-dependently with IC50 of 1.76 and 2.23 μm in RLMs, and 1.51 and 1.48 μm in HLMs, respectively. There was a mixed mechanism underlying such an inhibition effect. In rat, AUC(0–t), AUC(0–∞), Tmax and Cmax of buspirone and 6-OH buspirone increased significantly while co-administering with apatinib, but Vz/F and CLz/F decreased obviously while comparing group A with group B . Conclusions Apatinib suppresses the CYP450 based metabolism of buspirone in a mixed mechanism and boosted the blood exposure of prototype drug and 6-OH buspirone dramatically. Therefore, extra caution should be taken when combining apatinib with buspirone in clinic.

Aims Increased chemosensitivity to carbon dioxide (CO2 ) is an important trigger of central apnoeas (CA) in heart failure (HF), with negative impact on outcome. We hypothesized that buspirone, a 5HT1A receptor agonist that inhibits serotonergic chemoreceptor neuron firing in animals, can decrease CO2 chemosensitivity and CA in HF. Methods and results The BREATH study was a randomized, double-blind, placebo-controlled, crossover study (EudraCT-code 2015-005383-42). Outpatients with systolic HF (left ventricular ejection fraction 0.5 L/min/mmHg. The primary safety endpoint was freedom from serious adverse events. Sixteen patients (age 71.3 ± 5.8 years, all males, left ventricular ejection fraction 29.8 ± 7.8%) were enrolled. In the intention-to-treat analysis, more patients treated with buspirone (8/16, 50%) had a CO2 chemosensitivity reduction >0.5 L/min/mmHg from baseline than those treated with placebo (1/16, 6.7%) (difference between groups 43%, 95% confidence interval 14-73%, P = 0.016). Buspirone compared to baseline led to a 41% reduction in CO2 chemosensitivity (P = 0.001) and to a reduction in the AHI, central apnoea index and oxygen desaturation index of 42%, 79%, 77% at nighttime and 50%, 78%, 86% at daytime (all P 0.05). No patient reported buspirone-related serious adverse events. Conclusions Buspirone reduces CO2 chemosensitivity and improves CA and oxygen saturation across the 24 h in patients with HF.

Background: Angelman Syndrome (AS) is a congenital non inherited neurodevelopmental disorder. The contemporary AS management is symptomatic and it has been accepted that gene therapy may play a key role in the treatment of AS. Objective: The purpose of this study is to summarize existing and suggested gene therapy approaches to Angelman syndrome. Methods: This is a literature review. Pubmed and Scopus databases were researched with keywords (gene therapy, Angelman’s syndrome, neurological disorders, neonates). Peer-reviewed studies that were closely related to gene therapies in Angelman syndrome and available in English, Greek, Ukrainian or Indonesian were included. Studies that were published before 2000 were excluded and did not align with the aforementioned criteria. Results: UBE3A serves multiple roles in signaling and degradation procedures. Although the restoration of UBE3A expression rather than targeting known activities of the molecule would be the optimal therapeutic goal, it is not possible so far. Reinstatement of paternal UBE3A appears as an adequate alternative. This can be achieved by administering topoisomerase-I inhibitors or reducing UBE3A antisense transcript (UBE3A-ATS), a molecule which silences paternal UBE3A. Conclusion: Understanding UBE3A imprinting unravels the path to an etiologic treatment of AS. Gene therapy models tested on mice appeared less effective than anticipated pointing out that activation of paternal UBE3A cannot counteract the existing CNS defects. On the other hand, targeting abnormal downstream cell signaling pathways has provided promising rescue effects. Perhaps, combined reinstatement of paternal UBE3A expression with abnormal signaling pathways-oriented treatment is expected to provide better therapeutic effects. However, AS gene therapy remains debatable in pharmacoeconomics and ethics context.

Background: anxiety is a powerful central nervous system depression that can slow normal brain function. Buspirone is often prescribed to reduce the feelings of tension; this drug is also known as sedative drug. Aim of the work: this study aimed to detect the effect of buspirone hydrochloride on kidney of the pregnant rats and their foetuses (histological and histochemical studies). Material and methods: the current study was applied on thirty pregnant female rats that were categorized into three groups (ten pregnant rats in each group): Group1 (the control pregnant rats that were orally administrated with distilled water, group II (pregnant rats were given oral dosage of buspirone hydrochloride at dose level of 0.27 mg /100 g body weight /day daily for 15 days from the 6 th day to the 20th day of gestation and group III (pregnant rats were treated with buspirone hydrochloride at a dose level of 0.41 mg/100 gm body weight/day for 15 days from the 6 th to the 20th day of gestation. Kidney tissues were taken from pregnant rats and picked out from their foetuses of all groups which killed on the 20th day of gestation for the histological and histochemical studies. Results: maternal and foetal kidney tissues of both treated groups showed numerous changes post-treatment with buspirone that well-marked at the high concentration dose. Conclusion: the present study showed that administration of Buspirone drug resulted in several histological and histochemical alterations in the kidney tissues.

We investigated the influence of repeated peripheral inflammatory nociceptive stimulation of neonate female rats born to mothers exposed during pregnancy to chronic stress and the effect of an antidepressant drug fluoxetine, a selective serotonin (5-HT) reuptake inhibitor, and an anxiolytic drug buspirone, a 5-HT1A receptor agonist, on adaptive behavior and cognitive abilities of the offspring during the prepubertal period. The data on the effect of maternal stress exposure during the critical perinatal period of individual development on adaptive behavior and spatial learning abilities of the offspring provide support for the hypothesis on the possible beneficial effect of moderate stressful events experienced at an early age on stress tolerance in subsequent ontogenesis. The corrective effect of the above drugs on adaptive behavior and cognitive abilities of the prenatally stressed prepubertal female offspring exposed to repeated peripheral inflammatory pain at the neonatal stage is characterized.

Acute ethanol (EtOH) consumption exerts a biphasic effect on behavior and increases serotonin levels in the brain. However, the molecular mechanisms underlying alcohol-mediated behavioral responses still remain to be fully elucidated. Here, we investigate pharmacologically the involvement of the serotonergic pathway on acute EtOH-induced behavioral changes in zebrafish. We exposed zebrafish to 0.25, 0.5, 1.0% (v/v) EtOH for 1 h and analyzed the effects on aggression, anxiety-like behaviors, and locomotion. EtOH concentrations that changed behavioral responses were selected to the subsequent experiments. As a pharmacological approach, we used pCPA (inhibitor of tryptophan hydroxylase), WAY100135 (5-HT1A antagonist), buspirone (5-HT1A agonist), CGS12066A and CGS12066B (5-HT1B antagonist and agonist, respectively), ketanserin (5-HT2A antagonist) and (±)-DOI hydrochloride (5-HT2A agonist). All serotonergic receptors tested modulated aggression, with a key role of 5-HT2A in aggressive behavior following 0.25% EtOH exposure. Because CGS12066B mimicked 0.5% EtOH anxiolysis, which was antagonized by CGS12066A, we hypothesized that anxiolytic-like responses are possibly mediated by 5-HT1B receptors. Conversely, the depressant effects of EtOH are probably not related with direct changes on serotonergic pathway. Overall, our novel findings demonstrate a role of the serotonergic system in modulating the behavioral effects of EtOH in zebrafish. These data also reinforce the growing utility of zebrafish models in alcohol research and help elucidate the neurobiological mechanisms underlying alcohol abuse and associated complex behavioral phenotypes.

We studied the long-term effect of the combination of stress in the prenatal and prepubertal periods of development on indicators of tonic inflammatory pain in the formalin test and the depressive-like behavior, as well as on the stress reactivity of the hormonal response in adult rats. In addition, in rats of both sexes, the effect of serotonin reuptake inhibitor (5-HT) fluoxetine and 5-HT1A agonist buspirone, chronically administered to their stressed mothers during pregnancy, on the studied types of adaptive behavior disturbed by prenatal stress was evaluated. It was found that in rats of both sexes, prenatal stress intensified the pain response organized at the spinal and supraspinal levels of the central nervous system, fluoxetine and buspirone normalized them. Stress in the prepubertal period of development leveled the effect of prenatal stress on the inflammatory pain response integrated at the supraspinal level in adult rats; under these conditions, fluoxetine and buspirone did not act, unlike their antinociceptive effect on the pain response integrated at the spinal level. Stress in prepubertal age leveled the sex differences found in the depressive-like behavior in prenatally non-stressed and prenatally stressed rats with saline. In control adult females and adult females with prenatal effects, prepubertal stress increased plasma corticosterone after forced swimming compared to basal hormone levels, but no significant differences in the level of stress reactivity of the hormonal response after forced swimming were found. Thus, the conditions of stressful impacts that increase resistance to stress in adult rats are identified. Stress in critical periods of development forms a phenotype with increased stress resistance to inflammatory pain, which was found in the response organized at the supraspinal level in adults.

The effect of repeated peripheral inflammatory pain in newborn female rats, born to mothers subjected to chronic stress during pregnancy, was investigated on the adaptive behavior and cognitive abilities of the females when they reached prepubertal period of development. In addition, the effect of drugs (serotonin (5-HT) reuptake inhibitor antidepressant fluoxetine and an agonist 5-HT1A receptor anxiolytic buspirone) injected to the stressed pregnant dams was studied on the offspring behavior. The obtained new data on the effect of stress in the perinatal critical period of individual development on adaptive behavior and ability for spatial learning support the hypothesis of the possible beneficial effect of moderate stressful events at an early age on stress tolerance in subsequent ontogenesis. The effect of the applied drugs on the studied adaptive behavior and cognitive abilities of prenatally stressed offspring subjected to inflammatory pain in newborn state is characterized.

Treatment resistant depression (TRD) is associated with poor outcomes, but a consensus is lacking in the literature regarding which compound represents the best pharmacological augmentation strategy to antidepressants (AD). In the present review, we identify the available literature regarding the pharmacological augmentation to AD in TRD. Research in the main psychiatric databases was performed (PubMed, ISI Web of Knowledge, PsychInfo). Only original articles in English with the main topic being pharmacological augmentation in TRD and presenting a precise definition of TRD were included. Aripiprazole and lithium were the most investigated molecules, and aripiprazole presented the strongest evidence of efficacy. Moreover, olanzapine, quetiapine, cariprazine, risperidone, and ziprasidone showed positive results but to a lesser extent. Brexpiprazole and intranasal esketamine need further study in real-world practice. Intravenous ketamine presented an evincible AD effect in the short-term. The efficacy of adjunctive ADs, antiepileptic drugs, psychostimulants, pramipexole, ropinirole, acetyl-salicylic acid, metyrapone, reserpine, testosterone, T3/T4, naltrexone, SAMe, and zinc cannot be precisely estimated in light of the limited available data. Studies on lamotrigine and pindolol reported negative results. According to our results, aripiprazole and lithium may be considered by clinicians as potential effective augmentative strategies in TRD, although the data regarding lithium are somewhat controversial. Reliable conclusions about the other molecules cannot be drawn. Further controlled comparative studies, standardized in terms of design, doses, and duration of the augmentative treatments, are needed to formulate definitive conclusions.

NLX-101 and F13714 are selective, full efficacy, biased agonists of the 5-HT(1A) receptor. NLX-101 preferentially activates cortical post-synaptic 5-HT(1A) receptors whereas F13714 preferentially activates Raphe nuclei pre-synaptic 5-HT(1A) receptors. We compared NLX-101 and F13714 for their efficacy and potency to substitute for the discriminative cue produced by the prototypical, non-biased 5-HT(1A) receptor agonist, 8-OH-DPAT (racemate). Male and female Sprague-Dawley rats were trained to discriminate 8-OH-DPAT (0.1 mg/kg i.p., 20 min pre-treatment) from saline using a classical two-lever drug-discrimination procedure. 8-OH-DPAT (0.01 and 0.05 mg/kg i.p.) dose-dependently substituted for the training dose, with about 50 % responding on the 8-OH-DPAT-associated lever at 0.05 mg/kg. F13714 fully and very potently substituted for the training dose of 8-OH-DPAT from 0.018 mg/kg i.p., while NLX-101 only achieved full substitution at 0.5 mg/kg i.p., a dose which is known to also activate pre-synaptic 5-HT(1A) receptors. The 5-HT(1A) receptor partial agonist, buspirone, partially substituted (~80%) at 1 and 2 mg/kg i.p., doses which also decreased response rates. F13714 decreased response rates at 0.05 mg/kg. The selective 5-HT(1A) receptor antagonist WAY-100,635 (1 mg/kg s.c., 40 min pre-treatment) elicited almost no responding on the 8-OH-DPAT-associated lever by itself, but blocked the discriminative stimulus effects produced by administration (20 min pretreatment) of 8-OH-DPAT (0.1 mg/kg), F13714 (0.025 mg/kg), NLX-101 (0.5 mg/kg), or buspirone (1 mg/kg). These data suggest that the discriminative cue produced by 0.1 mg/kg i.p. 8-OH-DPAT results from activation of pre-synaptic 5-HT(1A) receptors. They also further demonstrate the distinct profiles in behavioral models of 5-HT(1A) receptor biased agonists.

Background: Generalized anxiety disorder (GAD) is one of the most common types of anxiety disorders with unclear pathogenesis. Our team’s previous research found that extensive neuronal apoptosis and neuronal regeneration disorders occur in the hippocampus of GAD rats. Danzhi Xiaoyao (DZXYS) Powder can improve the anxiety behavior of rats, but its molecular mechanism is not well understood.Objective: This paper discusses whether the pathogenesis of GAD is related to the abnormal expression of Notch signal pathway, and whether the anti-anxiety effect of DZXYS promotes nerve regeneration in the hippocampus by regulating the Notch signaling pathway.Methods: The animal model of GAD was developed by the chronic restraint stress and uncertain empty bottle stimulation method. After the model was successfully established, the rats in the model preparation group were divided into the buspirone, DZXYS, DZXYS + DAPT, and model groups, and were administered the corresponding drug intervention. The changes in body weight and food intake of rats were continuously monitored throughout the process. The changes in anxiety behavior of rats were measured by open field experiment and elevated plus-maze test, and morphological changes and regeneration of neurons in the rat hippocampus were observed by HE staining and double immunofluorescence staining. Changes in the expression of key targets of the Notch signaling pathway in the hippocampus were monitored by real-time fluorescence quantitative PCR and western blotting.Results: In this study, we verified that the GAD model was stable and reliable, and found that the key targets of the Notch signaling pathway (Notch1, Hes1, Hes5, etc.) in the hippocampus of GAD rats were significantly upregulated, leading to the increased proliferation of neural stem cells in the hippocampus and increased differentiation into astrocytes, resulting in neuronal regeneration. DZXYS intervention in GAD rats can improve appetite, promote weight growth, and significantly reverse the anxiety behavior of GAD rats, which can inhibit the upregulation of key targets of the Notch signaling pathway, promote the differentiation of neural stem cells in the hippocampus into neurons, and inhibit their differentiation into astrocytes, thus alleviating anxiety behavior.Conclusion: The occurrence of GAD is closely related to the upregulation of the Notch signaling pathway, which hinders the regeneration of normal neurons in the hippocampus, while DZXYS can downregulate the Notch signaling pathway and promote neuronal regeneration in the hippocampus, thereby relieving anxiety behavior.

Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of disability. While there continues to be expansive research in posttraumatic stress disorder (PTSD), depression and schizophrenia, there is a relative dearth of novel medications under investigation for anxiety disorders. This review's first aim is to summarize current pharmacological treatments (both approved and off-label) for panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and specific phobias (SP), including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), azapirones (e.g., buspirone), mixed antidepressants (e.g., mirtazapine), antipsychotics, antihistamines (e.g., hydroxyzine), alpha- and beta-adrenergic medications (e.g., propranolol, clonidine), and GABAergic medications (benzodiazepines, pregabalin, and gabapentin). Posttraumatic stress disorder and obsessive-compulsive disorder are excluded from this review. Second, we will review novel pharmacotherapeutic agents under investigation for the treatment of anxiety disorders in adults. The pathways and neurotransmitters reviewed include serotonergic agents, glutamate modulators, GABAergic medications, neuropeptides, neurosteroids, alpha- and beta-adrenergic agents, cannabinoids, and natural remedies. The outcome of the review reveals a lack of randomized double-blind placebo- controlled trials for anxiety disorders and few studies comparing novel treatments to existing anxiolytic agents. Although there are some recent randomized controlled trials for novel agents including neuropeptides, glutamatergic agents (such as ketamine and d-cycloserine), and cannabinoids (including cannabidiol) primarily in GAD or SAD, these trials have largely been negative, with only some promise for kava and PH94B (an inhaled neurosteroid). Overall, the progression of current and future psychopharmacology research in anxiety disorders suggests that there needs to be further expansion in research of these novel pathways and larger-scale studies of promising agents with positive results from smaller trials.

Post-fundoplication dyspepsia is a common complication of gastric fundoplication surgeries. This can be attributable to the loss of fundal relaxation, decreased gastric accommodation, and/or alterations in gastric motility and sensitivity following fundoplication. The role of neuromodulators in the management of such symptoms is unknown. We retrospectively assessed the efficacy of neuromodulators such as tricyclic antidepressants, buspirone, and mirtazapine for the management of post-fundoplication dyspepsia.

Raynaud's phenomenon (RP) is a medical condition characterized by vasospasm of the digital vessels in the fingers and toes. The prevalence of RP in the general population is estimated at 3-5% and can vary based on climate. It is classified into primary and secondary RP based on causality. RP has been reported in some cases diagnosed with coronavirus disease 2019 (COVID-19) infection. We report the case of a 14-year-old Caucasian female who presented during the pandemic with chief complaints of suicidal ideations and attempted suicide and had a history of attention-deficit hyperactivity disorder (ADHD) and persistent RP after a stimulant trial. After an initial failure of treatment with lisdexamfetamine, she was switched to methylphenidate hydrochloride (MPH). Within two months of starting MPH, the patient noticed skin discoloration of the lower legs and feet along with numbness. The discoloration of skin was mainly limited to her feet and gradually moved up her legs. She was advised to discontinue the MPH, but her symptoms persisted for four more months until her admission. Other etiologies were ruled out by multi-specialties and during her hospitalization. She was started on atomoxetine and buspirone with appropriate dose titration. Post-discharge from the hospital, no improvement was observed in the patient's RP at an outpatient follow-up performed within a month. The development of RP following MPH treatment and its persistence after stopping MPH is a fascinating event. Clinicians should be aware of the potential rare side effects of stimulants and stimulant-like medications, including vascular, hematological, and dermatological effects. Adolescents with ADHD may be particularly distressed by the COVID-19 pandemic and display increased behavioral issues. Stress can be a trigger for RP; therefore, minimizing stress in at-risk patients is essential.

BackgroundThe gold standard for symptomatic relief of Parkinson’s disease is L-DOPA. However, long-term treatment often leads to motor complications such as L-DOPA-induced dyskinesia (LID). While amantadine (Gocovri™) is the only approved therapy for dyskinesia in people with Parkinson’s disease on the American market, it is associated with neurological side effects and limited efficacy. Thus, there remains a high unmet need for addressing LID in Parkinson’s disease patients worldwide.ObjectiveThe objective of this study was to evaluate the efficacy, safety and performance compared to approved treatments of the serotonin receptor 1A (5-HT1A) and 5-HT1B/D agonists buspirone and zolmitriptan in the 6-hydroxydopamine unilaterally lesioned rat model for Parkinson’s disease.MethodsThe hemi-parkinsonian 6-OHDA lesioned rats underwent chronic treatment with L-DOPA to induce dyskinesia and were subsequently used for efficacy testing of buspirone, zolmitriptan and comparison with amantadine, measured as abnormal involuntary movement (AIM) scores after L-DOPA challenge. Safety testing was performed in model and naive animals using forelimb adjusting, rotarod and open field tests.Results5-HT1A and 5-HT1B/D agonism effectively reduced AIM scores in a synergistic manner. The drug combination of buspirone and zolmitriptan was safe and did not lead to tolerance development following sub-chronic administration. Head-to-head comparison with amantadine showed superior performance of buspirone and zolmitriptan in the model.ConclusionsThe strong anti-dyskinetic effect found with combined 5-HT1A and 5-HT1B/D agonism renders buspirone and zolmitriptan a potential clinical candidate for LID in Parkinson’s disease.

Objective: The aim of the study was to prepare and evaluate buccal-adhesive tablets of Buspirone HCl that avoid gastric degradation and first pass metabolism, thereby increasing the drug bioavailability and onset of action. Buspirone HCl belongs to a class anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Methods: In the present work, different ratios of Gantrez MS 955 along with Carbopol 934 were studied to give bioadhesive strength. A 32 full factorial design was applied to investigate the combined effect of concentration Carbopol 934 (X1) i.e. 5,7.5,10 mg and Gantrez MS 955 concentration (X2) i.e. 10,12.5,15 mg. Results: Results of the multiple regression analysis revealed that the independent variables significantly affected the dependent variables (bioadhesive strength (Y1), Q2 (Y2), Q3 (Y3), Q4 (Y4)). On the basis of multiple linear regression analysis and contour plot evaluation, it was found that combination of two polymers possessed excellent mucoadhesive properties allowing ease of application and removal of the tablets from the buccal mucosa. Conclusion: The formulation batch A9 fulfilled all the criteria set from the desirability search. From the in vitro diffusion study flux was calculated for the optimized batch. Study of the effect of tablet diameter and the environmental factors on the bioadhesion of the tablet was done. To study the environmental factor on bioadhesion, prehydration time and contact time were considered. Result found that increase in prehydration time decrease in bioadhesive strength and increase in contact time increased bioadhesive strength. Thus a stable Buccoadhesive formulation optimized for formulation ingredients and process parameters was prepared successfully.

Some studies have shown that augmenting buspirone with antidepressant has similar efficacy as the combination with two antidepressants in patients with major depressive disorder (MDD). Some researchers assume that the antidepressant boosting effect of buspirone is revealed under a poop-out state, which means a phenomenon where some patients having an initial response to an antidepressant may worsen or not improve any more even though they continue treatment because of serotonin depletion. Loudness dependence of auditory evoked potential (LDAEP) is a reliable marker of central serotonergic activity, and is inversely correlated with central serotonergic activity. Thus LDAEP will be a biological marker for prediction of treatment response with buspirone augmentation with SSRI because it can measure central serotonergic activity such as serotonin depletion. Two cases will be introduced and the literature evidence about whether LDAEP can predict the treatment response of buspirone augmentation in patients with MDD will be reviewed.

Co-morbid anxiety disorders, including generalized anxiety disorder (GAD), are highly prevalent among individuals with Williams syndrome (WS). However, reports of the pharmacologic treatment of only a limited number of previous anxiety disorders in WS have appeared in the literature. Here, we review the case histories of three adolescents/young adults with WS and the treatment course of co-morbid GAD with buspirone. Treatment with buspirone was well-tolerated and resulted in sustained response in all three cases. Common medical disorders in WS are highlighted with regards to safe and appropriate pharmacologic treatment of GAD. Buspirone's generally benign side effect profile is a major benefit of its use for treating GAD in individuals with WS.

Objective: The present study aims to formulate and evaluate Fast dissolving tablet of Buspirone, the drug that is used for management of anxiety, by direct compression method using various Super disintegrants. Methods: Ten formulations (F1-F10) of fast dissolving tablets of Buspirone were prepared by using various Superdisintegrants. The prepared tablets were evaluated for hardness, friability, thickness, drug content uniformity, water absorption, wetting time, and disintegration time and in vitro dissolution study. Results: Among all the formulations, F10 (containing 5 mg of Coprocessed (CS: SSG 1:2) Superdisintegrants) was considered to be the best formulation, which released up to 98% drug in 20 min as compared to a marketed conventional dosage form which dissolves in approx 60 min. The results of stability study of formulation F10 after a period of two months indicated that the formulation was stable. Conclusion: It was concluded that a fast-dissolving tablet of Buspirone containing various Superdisintegrants is better and effective to meet patient compliance.