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We report on a patient with ciltacabtagene autoleucel-induced movement and neurocognitive toxicity, which was refractory to immunosuppression but responsive to combination dopaminergic therapy (carbidopa/levodopa, ropinirole, amantadine). Response was seen upon both initial treatment and rechallenge after unintended withdrawal. This is the first report of a successful symptomatic treatment of this well-described neurotoxic syndrome. [ABSTRACT FROM AUTHOR]

In this paper, we report the synthesis, structural characterization, and antiviral properties of palladium(II) complexes with amantadine (atd) and memantine (mtn). Elemental and mass spectrometric analyses indicated a 1:2 metal/ligand ratio. The single crystal data for Pd‐mtn revealed that the complex adopts a square geometry with the two memantine ligands bonded to Pd(II) by the nitrogen atoms of the NH2 group, in a trans configuration. Computational studies supported a similar structure for Pd‐atd. The complexes were stable in DMSO solution for 24 h. The antiviral properties of Pd‐atd and Pd‐mtn were evaluated against Zika (ZIKV) and Chikungunya (CHIKV) viruses in vitro at their highest noncytotoxic concentrations. The Pd‐atd (at 2 µM) and Pd‐mtn (at 10 µM) complexes were able to impair 76% and 96% of CHIKV replication, respectively, which points the coordination of amantadine and memantine to Pd(II) as a successful strategy to increase their anti‐CHIKV properties. Conversely, the Pd(II) complexes did not significantly inhibit the replication of ZIKV, which confirms the selectivity towards CHIKV. Interaction of the compounds with N‐acetyl‐l‐cysteine, a model disulfide‐containing peptide, and plasmid DNA pointed to Cys‐containing peptides as more likely targets than nucleotides for the complexes. [ABSTRACT FROM AUTHOR]

Classical swine fever virus (CSFV) p7 viroporin plays crucial roles in cellular ion balance and permeabilization. The antiviral drug amantadine effectively inhibits viral replication by blocking the activity of CSFV p7 viroporin. However, little information is available for the binding mode of amantadine with CSFV p7 viroporin, due to the lack of a known polymer structure for CSFV p7. In this study, we employed AlphaFold2 to predict CSFV p7 structures. Subsequently, we conducted a docking study to investigate the binding sites of amantadine to CSFV p7. Computational analysis showed that CSFV p7 forms a pore channel in a hexameric structure. Furthermore, molecular dynamics (MD) simulations and mutant analyses further suggest that CSFV p7 likely exists as a hexamer. Docking studies and MD simulations showed that amantadine interacts with the hydrophibic regions of tetramer and pentamer, as well as with the hydrophobic pore channel of the hexamer. Considering the potential hexameric assembly of CSFV p7, along with docking results, MD simulations, and the characteristics of the gated ion channels, we propose a model of CSFV p7 ion channel based on its hexameric configuration. In this model, residues E21, Y25, and R34 are suggested to selectively recruit and dehydrate ions, while residues L28 and L31 likely act as hydrophobic constrictors, thereby restricting the free movement of water. The binding of amantadine to residues I20, E21, V24 and Y25 effectively blocks ion transport. However, this proposed molecular model requires experimental validation. Our findings give a structural insight into the models of CSFV p7 as an ion channel and provide a molecular explanation for the inhibition effects of amantadine on CSFV p7-mediated ion channel conductance. [ABSTRACT FROM AUTHOR]

Background: Methadone-induced sexual dysfunction in men can significantly impair their quality of life and reduce methadone adherence, thereby interfering with its therapeutic benefits. Objectives: This study aimed to compare the effects of bupropion and amantadine on reducing sexual dysfunction in methadone-dependent males. Methods: This clinical trial included 47 methadone-dependent males attending the Addiction Treatment Center in Babol, Iran. Participants were randomly assigned to either the amantadine group (n = 23) or the bupropion group (n = 24). Demographic data and addiction history were collected using a checklist, and sexual dysfunction was assessed with the International Index of Erectile Function (IIEF) Questionnaire before and after the intervention. Paired t-tests, independent t-tests, and chi-squared tests were used to compare the two groups. Results: Both groups had similar demographic variables and sexual function scores before the intervention (P > 0.05). However, there was a significant difference between the two groups in terms of total sexual dysfunction scores (52.13 ± 13.07 for bupropion vs. 60.79 ± 4.47 for amantadine; P = 0.006). Additionally, significant differences were observed in sexual desire (P = 0.003), satisfaction with intercourse (P = 0.001), and overall satisfaction (P = 0.034), with higher scores in the bupropion group. Adverse medication-related effects were less prevalent in the bupropion group (54.2%) compared to the amantadine group (60.9%). Conclusions: Bupropion appears to be more effective in improving sexual function in methadone-dependent males undergoing methadone treatment, with patients in the bupropion group achieving better scores than those in the amantadine group. Additionally, the occurrence of adverse effects was lower in the bupropion group compared to the amantadine group. [ABSTRACT FROM AUTHOR]

Abstract Classical swine fever virus (CSFV) p7 viroporin plays crucial roles in cellular ion balance and permeabilization. The antiviral drug amantadine effectively inhibits viral replication by blocking the activity of CSFV p7 viroporin. However, little information is available for the binding mode of amantadine with CSFV p7 viroporin, due to the lack of a known polymer structure for CSFV p7. In this study, we employed AlphaFold2 to predict CSFV p7 structures. Subsequently, we conducted a docking study to investigate the binding sites of amantadine to CSFV p7. Computational analysis showed that CSFV p7 forms a pore channel in a hexameric structure. Furthermore, molecular dynamics (MD) simulations and mutant analyses further suggest that CSFV p7 likely exists as a hexamer. Docking studies and MD simulations showed that amantadine interacts with the hydrophibic regions of tetramer and pentamer, as well as with the hydrophobic pore channel of the hexamer. Considering the potential hexameric assembly of CSFV p7, along with docking results, MD simulations, and the characteristics of the gated ion channels, we propose a model of CSFV p7 ion channel based on its hexameric configuration. In this model, residues E21, Y25, and R34 are suggested to selectively recruit and dehydrate ions, while residues L28 and L31 likely act as hydrophobic constrictors, thereby restricting the free movement of water. The binding of amantadine to residues I20, E21, V24 and Y25 effectively blocks ion transport. However, this proposed molecular model requires experimental validation. Our findings give a structural insight into the models of CSFV p7 as an ion channel and provide a molecular explanation for the inhibition effects of amantadine on CSFV p7-mediated ion channel conductance.

Objective We hypothesized that the administration of amantadine would increase awakening of comatose patients resuscitated from cardiac arrest. Methods We performed a prospective, randomized, controlled pilot trial, randomizing subjects to amantadine 100 mg twice daily or placebo for up to 7 days. The study drug was administered between 72 and 120 hours after resuscitation and patients with absent N20 cortical responses, early cerebral edema, or ongoing malignant electroencephalography patterns were excluded. Our primary outcome was awakening, defined as following two-step commands, within 28 days of cardiac arrest. Secondary outcomes included length of stay, awakening, time to awakening, and neurologic outcome measured by Cerebral Performance Category at hospital discharge. We compared the proportion of subjects awakening and hospital survival using Fisher exact tests and time to awakening and hospital length of stay using Wilcoxon rank sum tests. Results After 2 years, we stopped the study due to slow enrollment and lapse of funding. We enrolled 14 subjects (12% of goal enrollment), seven in the amantadine group and seven in the placebo group. The proportion of patients who awakened within 28 days after cardiac arrest did not differ between amantadine (n=2, 28.6%) and placebo groups (n=3, 42.9%; P>0.99). There were no differences in secondary outcomes. Study medication was stopped in three subjects (21.4%). Adverse events included a recurrence of seizures (n=2; 14.3%), both of which occurred in the placebo group. Conclusion We could not determine the effect of amantadine on awakening in comatose survivors of cardiac arrest due to small sample size.

The antiviral agent amantadine is frequently detected in seawater and marine organisms. Because of increasing concentrations, amantadine has become a contaminant of emerging concern. This compound has toxic effects on the brown algae Laminaria japonica. The effects of amantadine on the biological processes of L. japonica and the corresponding toxic mechanisms remain unclear. In this study, amantadine toxicity on L. japonica was investigated using histopathological and physiological characteristics combined with metabolomics analysis. Changes in metabolites were determined by untargeted metabolomics after exposure to 107 ng/L amantadine for 72 h. The catalase activity in the exposure group slightly increased, whereas the superoxide dismutase activity greatly decreased. An increase in the malondialdehyde concentration was observed after amantadine exposure, which suggested that lipid peroxidation and cell damage occurred. Metabolomics analysis showed that there were 406 differentially expressed metabolites after amantadine exposure. These were mainly phospholipids, amino acids, purines, and their derivatives. Inhibition of the glycerophospholipid metabolism affected the lipid bilayer and cell structure, which was aligned with changes in histological observation. Changes in amino acids led to perturbation of protein synthesis and induced oxidative stress through interference with glutathione metabolism and tyrosine metabolism. Amantadine also interfered with energymetabolismin L. japonica by disturbing the tricarboxylic acid cycle and purine metabolism. The results of this study provide new insights into the mechanism of amantadine toxicity on L. japonica. [ABSTRACT FROM AUTHOR]

Aims: This systematic review and meta-analysis aimed to assess the efficacy of NMDA antagonists in ASD (Autism Spectrum Disorder) on the core (communication and social interaction, repetitive behavior) and associated symptoms (irritability) of ASD, as well as their safety. Methods: PubMed, CENTRAL, CINHAL, EMBASE, and PsycINFO databases were searched until November 2023. Two authors independently selected the studies and extracted data. Randomized controlled trials assessing the efficacy of NMDA receptor antagonists in participants with ASD aged <18 years were included. The quality of the studies was assessed using the Risk of Bias-2 tool. A random-effect meta-analysis model was used to calculate standardized mean differences (SMD) or odds ratios (OR) using meta package in R. Results: This systematic review included ten studies (588 participants). Most studies did not report scales assessing core symptoms of ASD. Meta-analysis of efficacy on ASD core symptoms included three studies (248 participants). NMDA antagonists were not superior to placebo [SMD = 0.29; CI 95% (-1,94; 1.35); I² = 0%]. NMDA antagonists was not superior to placebo concerning response (four studies, 189 participants) [OR = 2.4; CI 95% (0.69; 8.38); I² = 35%]. Meta-analysis of efficacy on irritability included three studies (186 participants); NMDA antagonists were not superior to placebo [MD irritability = -1.94; CI 95% (-4.66; 0.77); I² = 0%]. Compared with placebo, significantly more participants in the NMDA antagonist group reported at least one adverse event (five studies, 310 participants) [OR = 2.04; CI 95% (1.17; 3.57); I² = 0%]. Conclusion: Current evidence does not support the effectiveness of NMDA antagonists in the treatment of ASD symptoms or irritability. Further research is needed due to the limited and low quality data available. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease (PD) patients harboring recessive gene variants exhibit a distinct clinical phenotype with an early disease onset and relatively mild symptoms. Data concerning individualized therapy for autosomal recessive PD forms are still scarce. Methods: Demographic and treatment data of a cohort of PD carriers of recessive genes (nine homozygous or compound heterozygous PRKN carriers, four heterozygous PRKN carriers, and three biallelic PINK1 carriers) were evaluated. Results: The average levodopa equivalent daily dose (LEDD) was 806.8 ± 453.5 (range 152–1810) in PRKN carriers and 765 ± 96.6 (range 660–850) in PINK1 carriers. The majority responded to low/moderate doses of levodopa. The response to dopamine agonists (DAs) was often favorable both as initial and longitudinal therapy. In total, 8/13 PRKN and 1/3 PINK1 carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate levodopa or DAs. Conclusions: In the era of personalized treatment, the therapeutic approach in recessive PD gene carriers might differ as compared to idiopathic PD. Lower LEDD doses were efficient even in patients with a very long disease duration, while a few patients were doing well without any levodopa treatment decades after disease initiation. DAs or amantadine could be used as a first and main line treatment regimen if well tolerated. Literature data on therapeutic strategies in carriers of pathogenic mutations in recessive PD genes, including device-aided treatments, will be further discussed. [ABSTRACT FROM AUTHOR]

Chronic fatigue syndrome (CFS) and neurocognitive deficits are a major problem of modern society. The etiology of CFS remains unclear, however, a large number of recent studies have shown oxidative stress may be involved in its pathogenesis. Fatigue is frequent and important in the lives of Parkinson's disease (PD) patients. 1-aminoadamantane (amantadine and memantine) derivatives has been proposed to be useful in the treatment of Parkinson's and Alzheimer's diseases. Its beneficial effect has been related to its novel properties as an N-methyl-D-aspartate receptor (NMDAR) blocker which can neutralize the effect of glutamate at striatal and subthalamic levels. We synthesized and evaluated the antioxidant activity of eleven new aminoadamantane derivatives. Their antioxidant activity has been evaluated using different (superoxide anion, hydroxyl) radical generating systems. The compound with s highest anti-oxidative capacity contain 2-(Benzhydrylsulfinyl) substituent. [ABSTRACT FROM AUTHOR]

Objective: To assess amantadine use and associated factors in the patients with Parkinson's disease (PD). Background: Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres. Methods: Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis). Results: Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12–18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users. Conclusions: About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs. [ABSTRACT FROM AUTHOR]

Objective: To quantify the benefits versus harms of amantadine in the treatment of irritability and aggression following traumatic brain injury. Methods: Secondary outcome data from a randomized controlled multisite trial of amantadine 100 mg twice daily were used to calculate number‐needed‐to‐treat (NNT). Given prior findings of positive clinician‐perceived effects and low incidence of adverse events, we hypothesized low number‐needed‐to‐treat for benefit (NNTB; high benefit) and high number‐needed‐to‐treat for harm (NNTH; low risk) based on the clinician ratings, supporting the use of amantadine in clinical practice. Specifically, NNTB values were calculated using number of individuals with improvement on the Clinician Global Impressions–Global Improvement scale (GI). NNTH values were computed using number of individuals with worsening on the GI and experiencing serious and any adverse events. Results: Based on clinician ratings, on average for every six patients treated with amantadine rather than placebo, one extra patient would be expected to improve (NNTB = 6.4; 95% confidence interval [CI]: [3.3–76.8]). More participants in the placebo group worsened than in the amantadine group, but the result was not statistically significant (NNTH = −92.4; 95% CI: [NNTB −32.9 to infinity to NNTH −19.2]). The amantadine and placebo groups did not differ on the numbers of adverse events experienced during the trial. Conclusion: Clinician ratings suggest modest benefit of amantadine 100 mg twice daily with low risk to appropriately selected patients with adequate renal clearance. Thus, amantadine should be considered a treatment option for the experienced brain injury clinician. These data may support treatment decisions when a pharmaceutical agent is being considered to control irritability/aggression. [ABSTRACT FROM AUTHOR]

Current therapies for depression are moderately effective, as response and remission rates were reported at 50% and 15-40%, following the first trial with current medications, respectively, and electroconvulsive therapy is not beneficial for more than half of the resistant patients. Recent research suggests that medication with glutamatergic modulatory properties may have antidepressant effects and would be of benefit to refractory patients. This study aims to review the efficacy of these medications in the treatment of unipolar depression. Ketamine, as the leading drug acting through the glutamatergic system, appears to be effective in treating depression IV and orally and in combination with electroconvulsive therapy. There is also clinical evidence of the promising effects of amantadine and lanicemine. Supplements and herbs such as L-carnosine, Crocus sativus (saffron), and Cinnamomum tamala, which were reported to be effective in randomized controlled trials on patients with depression, may act through this system as an antidepressant. Taken together, glutamate receptor modulators are alternative drugs for patients with resistant depression. Further high-quality clinical studies are recommended. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is an important global clinical issue, requiring not only prevention but also effective treatment. Following TBI, diverse parallel and intertwined pathological mechanisms affecting biochemical, neurochemical, and inflammatory pathways can have a severe impact on the patient's quality of life. The current review summarizes the evidence for the utility of amantadine in TBI in connection to its mechanism of action. Amantadine, the drug combining multiple mechanisms of action, may offer both neuroprotective and neuroactivating effects in TBI patients. Indeed, the use of amantadine in TBI has been encouraged by several clinical practice guidelines/recommendations. Amantadine is also available as an infusion, which may be of particular benefit in unconscious patients with TBI due to immediate delivery to the central nervous system and the possibility of precise dosing. In other situations, orally administered amantadine may be used. There are several questions that remain to be addressed: can amantadine be effective in disorders of consciousness requiring long-term treatment and in combination with drugs approved for the treatment of TBI? Do the observed beneficial effects of amantadine extend to disorders of consciousness due to factors other than TBI? Well-controlled clinical studies are warranted to ultimately confirm its utility in the TBI and provide answers to these questions. [ABSTRACT FROM AUTHOR]

Background/Aim: A few case reports of central nervous system (CNS) symptoms caused by amantadine intoxication have been published, detailing various types of symptoms and differing times to onset. We encountered a patient who developed CNS symptoms with amantadine. This prompted us to investigate the types, time to onset, and outcome of CNS adverse reactions to amantadine by analyzing data from a pharmacovigilance database. Patients and Methods: The patient was evaluated at Chutoen General Hospital, Shizuoka, Japan. Analysis was performed using the Japanese Adverse Drug Event Report (JADER) database. Results: In our case, the amantadine blood concentration was 4,042 ng/ml, i.e., in the toxic range. The time to onset was 26 days for dyskinesia and 90 days for depressed level of consciousness. Symptoms resolved when amantadine was discontinued. The JADER database contained 974 cases of adverse reactions to amantadine. The most frequently reported CNS adverse reaction was hallucination, with a reporting odds ratio of 64.28 (95% confidence interval=52.67-78.46). Positive signals were detected for all CNS adverse reactions. For all CNS reactions, clinical outcomes were poor in a comparatively low percentage of cases. Most CNS reactions occurred soon after administration of amantadine, usually within approximately one month. Conclusion: Because most CNS adverse reactions to amantadine usually occur within approximately one month of initiating treatment, healthcare providers should exercise heightened vigilance in monitoring patients for such reactions during this period. [ABSTRACT FROM AUTHOR]

Amantadine, despite being on the market for 55 years, has several unknown aspects of its pharmacokinetics especially related to the influence of covariates such as age, disease, or interactions linked to amantadine's renal elimination. As amantadine is used in Parkinson's disease and is considered a potential candidate in COVID treatment and other diseases, there is an unmet need for thorough understanding of its pharmacokinetic in special populations, such as the elderly. We aimed to mechanistically describe amantadine pharmacokinetics in healthy subjects and shed some light on the differences in drug behavior between healthy volunteers (18–65 years) and an elderly/geriatric population (65–98 years) using PBPK modeling and simulation. The middle‐out PBPK model includes mechanistic description of drug renal elimination, specifically an organic cation transporter (OCT)2‐mediated electrogenic bidirectional transport (basolateral) and multidrug and toxic compound extrusion (MATE)1‐mediated efflux (apical). The model performance was verified against plasma and urine data reported after single and multiple dose administration in healthy volunteers and elderly patients from 18 independent studies. The ratios of predicted vs. observed maximal plasma concentration and area under the concentration–time curve values were within 1.25‐fold. The model illustrates that renal transporter activity is expected to decrease in healthy elderly compared to healthy volunteers, which is in line with literature proteomic data for OCT2. The model was applied to assess the potential of reaching toxicity‐related plasma concentrations in different age groups of geriatric subjects. [ABSTRACT FROM AUTHOR]

The present study describes an “one-step” derivatization and microextraction using a pH-switchable hydrophilicity solvent for the determination of amantadine and memantine in human urine by liquid chromatography and fluorescence detection. The procedure is based on the derivatization of the analytes with o-phthalaldehyde/N-acetyl cysteine at alkaline conditions in the presence of sodium salicylate as extractant in a homogeneous solution. The liquid-solid transition of salicylic acid was achieved by adding an aliquot of concentrated phosphoric acid that enables efficient dispersion and phase separation in a single step. Due to the moderate melting point of salicylic acid, its solidification is carried out at room temperature without the need for sample cooling. Critical parameters affecting the efficiency of the derivatization reaction and the microextraction performance were investigated and optimized. The fluorescent analyte derivatives were monitored at λex/λem = 340/450 nm. The proposed method was validated in terms of specificity, linearity, precision and trueness. The method was linear in the range of 50–2000 ng mL−1 while the intraday and between days precision was less than 13.7% in all cases. The trueness of the method ranged between 87.9 and 113%. The green character and the applicability of the method were assessed using ComplexMoGAPI and BAGI tools. The developed analytical scheme presented satisfactory performance, and it could be applied in the analysis of selected drugs in human urine samples.

Objective: To understand how methylphenidate (MPH) is used in youth with traumatic brain injury (TBI) during inpatient pediatric rehabilitation. Setting: Inpatient pediatric rehabilitation. Participants: In total, 234 children with TBI; 62 of whom received MPH and 172 who did not. Patients were on average 11.6 years of age (range, 2 months to 21 years); 88 of 234 were female; the most common mechanism of injury was motor vehicle collision (49%); median (IQR) acute hospital length of stay (LOS) and inpatient rehabilitation LOS were 16 (10-29) and 23 (14-39), respectively; 51 of 234 were in a disorder of consciousness cognitive state at time of inpatient rehabilitation admission. Design: Multicenter, retrospective medical record review. Main Measure(s): Patient demographic data, time to inpatient pediatric rehabilitation admission (TTA), cognitive state, MPH dosing (mg/kg/day). Results: Patients who received MPH were older (P =.011); TTA was significantly longer in patients who received MPH than those who did not (P =.002). The lowest recorded dose range by weight was 0.05 to 0.89 mg/kg/d, representing an 18-fold difference; the weight-based range for the maximum dose was 0.11 to 0.97 mg/kg/d, a 9-fold difference. Patients in lower cognitive states at admission (P =.001) and at discharge (P =.030) were more likely to receive MPH. Five patients had side effects known to be associated with MPH; no serious adverse events were reported. Conclusion: This multicenter study indicates that there is variable use of MPH during acute inpatient rehabilitation for children with TBI. Children who receive MPH tend to be older with lower cognitive states. Dosing practices are likely consistent with underdosing. Clinical indications for MPH use during inpatient pediatric rehabilitation should be better defined. The use of MPH, as well as its combination with other medications and treatments, during inpatient rehabilitation needs to be further explored. [ABSTRACT FROM AUTHOR]

Practical relevance: Chronic pain is a significant welfare concern in cats, and neuropathic pain, which arises from aberrant processing of sensory signals within the nervous system, is a subcategory of this type of pain. To comprehend this condition and how multimodal pharmacotherapy plays a central role in alleviating discomfort, it is crucial to delve into the anatomy of nociception and pain perception. In addition, there is an intricate interplay between emotional health and chronic pain in cats, and understanding and addressing the emotional factors that contribute to pain perception, and vice versa, is essential for comprehensive care. Clinical approach: Neuropathic pain is suspected if there is abnormal sensation in the area of the distribution of pain, together with a positive response to trial treatment with drugs effective for neuropathic pain. Ideally, this clinical suspicion would be supported by confirmation of a lesion at this neurolocalisation using diagnostic modalities such as MRI and neuroelectrophysiology. Alternatively, there may be a history of known trauma at that site. A variety of therapies, including analgesic, anti-inflammatory and adjuvant drugs, and neuromodulation (eg, TENS or acupuncture), can be employed to address different facets of pain pathways. Aim: This review article, aimed at primary care/ general practitioners, focuses on the identification and management of neuropathic pain in cats. Three case vignettes are included and a structured treatment algorithm is presented to guide veterinarians in tailoring interventions. Evidence base: The review draws on current literature, where available, along with the author's extensive experience and research. [ABSTRACT FROM AUTHOR]

A simple, Accurate, precise method was developed for the estimation of the Amantadine in bulk and pharmaceutical dosage form. Chromatogram was run through ACQUITY UPLC BEH C18 Column, 1.7 µm, 2.1 mm X 50 mm. Mobile phase containing 0.1% AmmoniumFormate: Methanol taken in the ratio 73.6 (%v/v) and 26.3 was pumped through column at a flow rate of 0.28 ml/min. Temperature was maintained at 29.21°C. Optimized wavelength selected was ACQUITY TUV ChA 219 nm. Retention time of Amantadine was found to be 1.814 min. %RSD of the Amantadine was found to be 0.4%. %Recovery was obtained as 99.94% for Amantadine. LOD, LOQ values obtained from regression equations of Amantadine were 0.05, 0.15. Regression equation of Amantadine is y = 52995x + 2524.1. with regression coefficient value is found to be 0.99. Retention times were decreased and that run time was decreased, so the method developed was simple and economical that can be adopted in regular Quality control test in Industries. [ABSTRACT FROM AUTHOR]

Parkinson's disease is second most common neurodegenerative disorder neurological illness that primarily affects patients in their later years of life. Specific neurons in the brain begin to malfunction resulting in a loss of a substance called dopamine which is characterized by the accumulation of α-synuclein aggregates within cells, forming structures known as Lewy bodies and Lewy neurites. It is affecting more than 1% of people worldwide (aged 65 and above) and is expected to increase in prevalence by 2030. Muscle rigidity, tremor, and unresponsiveness of motion are some of the motor signs of this condition, and on another hand pain, despair, and anxiety are some examples of non-motor symptoms. Levodopa, pramipexole, ropinirole, alprazolam, benztropine, trihexyphenidyl, and many more drugs are used to treat symptoms of Parkinson's disease. Among them, the most common surgical symptomatic treatment is levodopa, which has better quality-of-life improvements in early Parkinson's disease than other medications. Still, the success rate of medication is 14.9% only. Other than these patients are also treated with non-medications which are known as therapies like yoga, massage, music, and so on. As per the literature, most studies reveal that the therapies improved the quality of life by up to 58%. So, researchers need to be focused on the synthesis of novel drugs that create a high impact on the treatment of Parkinson's disease. In this review paper, we discuss the pharmacological treatments for PD and discuss some of the current treatments. We hope this review article encourages the researchers to work in this field and develop new drugs against PD or permanent treatment for the person suffering from Parkinson. [ABSTRACT FROM AUTHOR]

Antibiotics treat bacterial infections, whereas antiviral drugs treat viral illnesses. Antivirals are used to treat a variety of infectious diseases, including COVID-19 and influenza. The technique of reversed-phase high-performance liquid chromatography (RP-HPLC) provides more sensitivity and precision than other approaches, particularly spectrophotometric. This research seeks to develop a simple method for simultaneously quantifying acyclovir, amantadine, and oseltamivir in creams and capsules. The RP-HPLC method optimization and development for verifying the separation and quantification of three antiviral drugs included the investigation of the optimal buffer concentration, pH value, and acetonitrile content. On a C8 HyperClone BDS column, the RP-HPLC system with UV detection achieved separation (250 x 4.60 mm, 130A, and 5). The mixture of acetonitrile and acetate buffer as mobile phase gradient elution at a detection wavelength of 254 nm and 1 mL/min flow rate. The proposed method provided a linear range of 0.08-10.5, 0.06-4.5 and 0.02-14 μg/mL, as well as excellent validated values for LOD (0.0205, 0.0107, and 0.0083 μg/mL) and LOQ (0.0621, 0.0324 and 0.0251 μg/mL) with a coefficient of determination (r2) of the regression line of 0.9998, 0.9988, and 0.9994 for acyclovir, amantadine, and oseltamivir, respectively. [ABSTRACT FROM AUTHOR]

AimsThis systematic review and meta-analysis aimed to assess the efficacy of NMDA antagonists in ASD (Autism Spectrum Disorder) on the core (communication and social interaction, repetitive behavior) and associated symptoms (irritability) of ASD, as well as their safety.MethodsPubMed, CENTRAL, CINHAL, EMBASE, and PsycINFO databases were searched until November 2023. Two authors independently selected the studies and extracted data. Randomized controlled trials assessing the efficacy of NMDA receptor antagonists in participants with ASD aged

Abstract Background Connective tissue involvement in a mitochondrial disorder has been only rarely reported. Case presentation A 32-year-old female with Leigh-like syndrome extending into adulthood due to the mtDNA variant m.10191 T > C developed various connective tissue abnormalities, which manifested as hyperlaxity of joints, decreased clivo-axial angle, subluxations of various joints, scoliosis, hyperextensibility of skin (stretchy skin), easy tearing, papyraceous scarring, frequent petechiae, very easy bruising, impaired wound healing, blood pooling in feet, and tiny veins. She received symptomatic treatment and physiotherapy, which provided some sort of relief. Conclusions The phenotypic spectrum of the m.10191 T > C variant is broader than previously anticipated.

An important drug used in the treatment of Parkinson’s disease is amantadine. We are the first to perform a comprehensive study based on various glycation and oxidation factors, determining the impact of amantadine on protein glycoxidation. Sugars (glucose, fructose, galactose) and aldehydes (glyoxal, methylglyoxal) were used as glycation agents, and chloramine T was used as an oxidant. Glycoxidation biomarkers in albumin treated with amantadine were generally not different from the control group (glycation/oxidation factors), indicating that the drug did not affect oxidation and glycation processes. Molecular docking analysis did not reveal strong binding sites of amantadine on the bovine serum albumin structure. Although amantadine poorly scavenged hydroxyl radical and hydrogen peroxide, it had significantly lower antioxidant and antiglycation effect than all protein oxidation and glycation inhibitors. In some cases, amantadine even demonstrated glycoxidant, proglycation, and prooxidant properties. In summary, amantadine exhibited weak antioxidant properties and a lack of antiglycation activity.

Simple Summary: Amantadine, a drug initially used as an antiviral agent to treat the influenza A virus (though currently, its main application is in the treatment of Parkinson's disease) has also been used to control pain due to its mechanism of action: exerting non-competitive antagonism N-methyl-D-aspartate (NMDA) glutamatergic receptors, which participate in the neurophysiological project of pain via the inhibition of central sensitization. We hope that our study makes a significant contribution to the literature because the preemptive oral administration of amantadine at a dose of 5 mg/kg resulted in superior postsurgical pain control. In addition, the administration of amantadine did not result in cardiovascular or respiratory alterations or adverse effects during the intraoperative period of OVH in the evaluated cats. This study aimed to evaluate the effect of the preemptive administration of amantadine on postoperative analgesia in cats undergoing ovariohysterectomy and its influence on the physiological parameters. Twenty healthy domestic cats scheduled to undergo ovariohysterectomy at the Santa Cruz State University, Ilhéus, were divided into two groups: the control group (Group C; n = 10) and the amantadine group (Group A; n = 10). The cats in Group C received placebo capsules 30 min prior to the standard anesthetic protocol, whereas those in Group A received 5 mg/kg of amantadine orally 30 min prior to the standard anesthetic protocol. Postoperative pain was assessed using the visual analog scale and the UNESP-Botucatu multidimensional scale for the evaluation of postoperative pain in cats. The administration of amantadine had no effect on the physiological parameters evaluated. The pain scores in Group A were lower than those in Group C, indicating that the frequency of rescue analgesic administration cats in Group A was lower. That way, preemptive oral administration of amantadine at a dose of 5 mg/kg was effective at controlling postoperative pain in cats undergoing ovariohysterectomy. Moreover, no adverse effects or alterations in the physiological patterns were observed in the treated animals. [ABSTRACT FROM AUTHOR]

Background: Increased activity across corticostriatal glutamatergic synapses may contribute to L-DOPA-induced dyskinesia in Parkinson's disease. Given the weak efficacy and side-effect profile of amantadine, alternative strategies to reduce glutamate transmission are being investigated. Metabotropic glutamate receptor 4 (mGlu4) is a promising target since its activation would reduce glutamate release. Objective: We hypothesized that two mGlu4 positive allosteric modulators, Lu AF21934 ((1 S,2 R)-N1-(3,4-dichlorophenyl)cyclohexane-1,2-dicarboxamide) and ADX88178 (5-Methyl-N-(4-methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)thiazol-2-amine), would provide relief in rat and primate models of L-DOPA-induced dyskinesia. Methods: The ability of Lu AF21934 or ADX88178 to reverse pre-established dyskinesia was examined in L-DOPA-primed 6-hydroxydopamine-lesioned rats expressing abnormal involuntary movements (AIMs) or in 1-methyl-4-phenyl,1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets expressing L-DOPA-induced dyskinesia. Additionally, the ability of Lu AF21934 to prevent the development of de novo L-DOPA-induced AIMs was explored in the 6-hydroxydopamine-lesioned rats. Results: Neither Lu AF21934 (10 or 30 mg/kg p.o.) nor ADX88178 (10 or 30 mg/kg p.o.) reduced pre-established AIMs in 6-hydroxydopamine-lesioned rats. Similarly, in L-DOPA-primed common marmosets, no reduction in established dyskinesia was observed with Lu AF21934 (3 or 10 mg/kg p.o.). Conversely, amantadine significantly reduced (>40%) the expression of dyskinesia in both models. Lu AF21934 also failed to suppress the development of AIMs in 6-hydroxydopamine-lesioned rats. Conclusions: This study found no benefit of mGlu4 positive allosteric modulators in tackling L-DOPA-induced dyskinesia. These findings are concordant with the recent failure of foliglurax in phase II clinical trials supporting the predictive validity of these pre-clinical dyskinesia models, while raising further doubt on the anti-dyskinetic potential of mGlu4 positive allosteric modulators. [ABSTRACT FROM AUTHOR]

To develop effective pharmaceutical formulations using supercritical carbon dioxide (scCO2) techniques, it is necessary to obtain the solubility of the medicinal ingredients in scCO2. In the current study, the solubility of Amantadine in scCO2 was evaluated under 28 different operating conditions involving seven pressures and four temperatures. To theoretically study this process, some popular empirical models and two well‐known thermodynamic models (PR‐WS and PC‐SAFT) were examined. The results suggest that the PR‐WS and PC‐SAFT models are the most accurate in establishing a correlation of the solubility of Amantadine in scCO2. [ABSTRACT FROM AUTHOR]

Introduction: Traumatic brain injury (TBI) is one of the most common causes of death and an important burden to the worldwide healthcare system and society. There is a lack of guidelines for types of monitoring or neuroprotective therapy. The aim of this pilot study was to assess its feasibility and, furthermore, to evaluate the impact of Cerebrolysin on the following clinical outcomes: length of stay, Glasgow Outcome Scale (GOS) and mortality. Methods: A cohort of 56 patients was included in this non-randomised, real-time, pre–post-interventional study. The patients were assessed with the Glasgow Coma Scale (GCS) and divided into two groups: severe (GCS < 8) and non-severe (GCS > 8). After the radiological examination (CT scan), the patients were qualified for an immediate neurosurgical procedure if needed. The patients were admitted to the intensive care unit, where a standardised protocol for TBI treatment was implemented. Additional neuromonitoring was applied. Results: There were 56 patients (19 females; 33.9%), of which 41 were considered severe cases; the patients were allocated to the Cerebrolysin (n = 25) or control groups (n = 31). In a generalised linear model (GLM) approach, the use of Cerebrolysin was associated with a decrease in the probability of death in non-severe patients (by 0.333 (standard error (SE) = 0.157, p = 0.034)) but not in severe patients (estimate (Est.) = −0.115, SE = 0.127, p = 0.364). Patients who received Cerebrolysin and who were neuromonitored had favourable outcomes and better survival rates. Conclusions: A multimodal treatment approach with monitoring and Cerebrolysin may have a beneficial effect on patients with less severe TBIs; however, the present study has multiple limitations, and further research is needed. [ABSTRACT FROM AUTHOR]

Many COVID-19 survivors experience lingering post-COVID-19 symptoms, notably chronic fatigue persisting for months after the acute phase. Despite its prevalence, limited research has explored effective treatments for post-COVID-19 fatigue. This randomized controlled clinical trial assessed the impact of Amantadine on patients with post-COVID-19 fatigue. The intervention group received Amantadine for two weeks, while the control group received no treatment. Fatigue levels were assessed using the Visual Analog Fatigue Scale (VAFS) and Fatigue Severity Scale (FSS) questionnaires before and after the trial. At the study's onset, VAFS mean scores were 7.90 ± 0.60 in the intervention group and 7.34 ± 0.58 in the control group (P-value = 0.087). After two weeks, intervention group scores dropped to 3.37 ± 0.44, significantly lower than the control group's 5.97 ± 0.29 (P-value < 0.001). Similarly, FSS mean scores at the trial's commencement were 53.10 ± 5.96 in the intervention group and 50.38 ± 4.88 in the control group (P-value = 0.053). At the trial's end, intervention group scores decreased to 28.40 ± 2.42, markedly lower than the control group's 42.59 ± 1.50 (P-value < 0.001). In this study, we report the safety, tolerability, and substantial fatigue-relieving effects of Amantadine in post-COVID-19 fatigue. The intervention demonstrates a statistically significant reduction in fatigue levels, suggesting Amantadine's potential as an effective treatment for this persistent condition. [ABSTRACT FROM AUTHOR]

The synthesis of new compounds for the treatment of infectious diseases remains one of the challenging tasks of the modern world. The prime focus of this research is to take action on amantadine-based derivatives synthesised by multicomponent Ugi reaction. Ugi reaction is widely used in the synthesis of biologically active compounds. It is an efficient and useful method of synthesis to prepare different types of bonds and compounds, such as peptide-like compounds, different natural products, heterocyclic derivatives, and low molecular drug-like compounds. Ugi reaction includes four compounds: acids, aldehyde or ketone, amine, and isonitrile. Adamantane is considered an interesting field of research due to its exceptional qualities. Adamantane derivatives are actively used in pharmaceutical industry due to their durable properties. Its derivatives are powerful compounds in a wide range of applications from systemic to topical therapy. In this study, some new amantadine (1-amino adamantane) moiety-containing compounds were synthesised via multicomponent Ugi reaction by using amanatadine, ethyl isocyanoacetate, some aldehydes, and carboxylic acids and corresponding dipeptide-like derivatives were isolated. The structure of the synthesised compounds was established by IR, NMR and LC-MS measurements. Synthesised compounds were studied for their antimicrobial activity against 10 different bacterial species using disk diffusion methods. [ABSTRACT FROM AUTHOR]

Background and purpose: Adamantanes were listed as an interesting option as an early intervention against COVID‐19. We aimed to evaluate the effectiveness of amantadine in preventing the progression of COVID‐19 and its neurological sequelae. Methods: Unvaccinated patients with confirmed SARS‐CoV‐2 infection within 5 days were enrolled. Subjects were randomized (50:50) to amantadine (AMD; 100 mg twice daily) or placebo (PLB) for 14 days. The Ordinal Scale for Clinical Improvement of the World Health Organization (OSCI‐WHO) was the primary measure. Secondary endpoints included assessment for fatigue; depression, disorders of smell and taste, and sleepiness on Days 1 and 15. Results: We enrolled 99 patients (49 AMD and 50 PLB). Disease progression (OSCI‐WHO = 4) was observed in 6% (AMD) and 8% (PLB) patients (p > 0.05) with further deterioration (OSCI‐WHO〉4) in 0% (AMD) and 8% (PLB) patients (p > 0.05). Complete recovery on Day 15 was 60% higher in the AMD compared with the PLB group (p = 0.025). There was improvement in taste (AMD: p = 0.003; PLB: p = 0.0001) and smell (AMD: p = 0.005; PLB: p = 0.0004) but not in fatigue in both groups. Improvement was observed in the AMD (p = 0.010) but not in the PLB group (p = 0.058) when assessing depression as well as sleepiness (AMD: p = 0.0002; PLB: p = 0.341). There was one death in the PLB group (2.0%) and none in the AMD group (p > 0.05) until Day 210. Overall, the drug was well tolerated. Conclusion: The central effects of amantadine on the nervous system with reduction of sleepiness and depression might have had a supportive effect on faster recovery in early COVID‐19 patients. [ABSTRACT FROM AUTHOR]

Amantadine (AMD) is an antiviral drug that is prohibited for use in livestock and poultry. In this study, carboxyl-modified magnetic nanoparticles (MNPs) were synthesized using the solvothermal method in one step with harmless and inexpensive regents, and they were used to label monoclonal antibodies (mAbs) of AMD in microwells with electrostatic adsorption. Then, a magnetic immunochromatography assay (MICA) method was successfully established. Under optimal conditions, the MICA showed a good performance, with a linear range of 0.2~10.0 µg/L. The limit of detection (LOD) was 0.068 µg/L with the instrument, and the visual LOD (vLOD) was 0.5 µg/L. There was no cross-reaction with rimantadine and ribavirin. The vLOD in real samples was 1.0 µg/kg. The developed MICA has the advantages of convenience, speed, and sensitivity, which make it suitable for the on-site rapid detection of AMD residues in chicken tissues and eggs. [ABSTRACT FROM AUTHOR]

In the United States and Europe, the drug Memantine, Food and Drug Administration (FDA) approves a partial antagonist of the N-methyl-d-aspartate receptor (NMDAR), for the treatment of Alzheimer's disease (AD). Memantine may also be useful in treating other neurological disorders, such as dementia and Parkinson's disease (PD). As a neuroprotectant, memantine has been shown to have a favourable effect on both neurodegenerative and vascular processes in animal studies. Memantine--a partial NMDAR antagonist--blocks NMDA glutamate receptors to regulate the glutamatergic system and ease cognitive and memory issues while large quantities of glutamate induce neurodegeneration. For memantine to be effective, it must connect with the NMDAR in an uncompetitive manner, allowing the receptor's physiological function to be preserved while also ensuring that memantine is safe and has a low adverse-event profile. It's possible that memantine might be beneficial in the treatment of Parkinson's disease, since NMDAR antagonism has been implicated in the disease's pathophysiology, and no other medicine is effective enough to replace L-dopa. In spite of its mild side effects, memantine has only been demonstrated to produce a slight reduction in AD and VD, and hence attempts are being made to build new and more powerful memantine-based medications to perhaps provide higher effectiveness. In June 2021, the FDA authorized Aducanumab for medicinal use in the United States. The first-of-its-kind therapy for Alzheimer's disease and the first novel treatment for Alzheimer's since 2003 have been authorised by the FDA. [ABSTRACT FROM AUTHOR]

Background: Connective tissue involvement in a mitochondrial disorder has been only rarely reported. Case presentation: A 32-year-old female with Leigh-like syndrome extending into adulthood due to the mtDNA variant m.10191 T > C developed various connective tissue abnormalities, which manifested as hyperlaxity of joints, decreased clivo-axial angle, subluxations of various joints, scoliosis, hyperextensibility of skin (stretchy skin), easy tearing, papyraceous scarring, frequent petechiae, very easy bruising, impaired wound healing, blood pooling in feet, and tiny veins. She received symptomatic treatment and physiotherapy, which provided some sort of relief. Conclusions: The phenotypic spectrum of the m.10191 T > C variant is broader than previously anticipated. [ABSTRACT FROM AUTHOR]

Objective: This research aimed to assess the effectiveness of combination therapy with amantadine and clonidine against clonidine alone on subjective opioid withdrawal symptoms in patients treated with buprenorphine. Methods and Materials: Patients were recruited from outpatient addiction treatment centers for this double-blind, randomized control trial. They were divided into two groups randomly assigned to receive either clonidine (0.15–0.3 mg/day) or clonidine with amantadine (100–200 mg/day). We assessed withdrawal symptoms with the Subjective Opiate Withdrawal Scale (SOWS) on the first day of admission and 3, 7, 14, and 21 days afterward. Results: Forty-three patients completed the trial in each group. The impact of adding-on amantadine on the mean SOWS compared to control was significant (p < .001) at any time of the study period. However, there were no significant differences in mean SOWS within groups during follow-up (p > .05). Also, there were no significant differences in mean SOWS between the two groups during follow-up time (day 3rd, 7th, 14th, and 21st) (p > .05). Conclusion: Amantadine and clonidine combined treatment would result in fewer opioid withdrawal symptoms than clonidine alone, with a decrease commencing on the third day. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common neurodegenerative illness worldwide. It is an age-related sickness. An illness treatment plan is urgently required. Such secondary metabolites from plants may undoubtedly be the source of the medications with less adverse effects. 6-Hydroxydopamine (6-OHDA) is used experimentally to mimic Parkinson's disease in adult zebrafish. In the realm of medicine, there are no ideal cures for ailments. For the past few decades, a number of plant secondary chemicals have been tested in preclinical settings to cure this illness. Many references have been made to cyclotide's neuroprotective, anti-inflammatory, and antioxidant properties. Furthermore, it has recently been demonstrated that amantadine (AMA), an aminoadamantane well-known for its mild antiparkinsonian action, counteracts central nervous system dysfunction. Apart from oxidative stress and mitochondrial damage, 6-OHDA may also cause decreased cytosolic levels of Tyrosine Hydroxylase (TH). Since this is primarily thought to be in charge of dopamine production in the central nervous system, an antagonist of TH may be the best medication option when treating Parkinson's disease. Since Amantadine (AMA) is the conventional medication, the current study compares the potential of Cyclotide as Tyrosine Hydroxylase Inhibitors to examine the molecular anti-TH interactions in 6-OHDA-induced adult zebrafishes. [ABSTRACT FROM AUTHOR]

An important drug used in the treatment of Parkinson's disease is amantadine. We are the first to perform a comprehensive study based on various glycation and oxidation factors, determining the impact of amantadine on protein glycoxidation. Sugars (glucose, fructose, galactose) and aldehydes (glyoxal, methylglyoxal) were used as glycation agents, and chloramine T was used as an oxidant. Glycoxidation biomarkers in albumin treated with amantadine were generally not different from the control group (glycation/oxidation factors), indicating that the drug did not affect oxidation and glycation processes. Molecular docking analysis did not reveal strong binding sites of amantadine on the bovine serum albumin structure. Although amantadine poorly scavenged hydroxyl radical and hydrogen peroxide, it had significantly lower antioxidant and antiglycation effect than all protein oxidation and glycation inhibitors. In some cases, amantadine even demonstrated glycoxidant, proglycation, and prooxidant properties. In summary, amantadine exhibited weak antioxidant properties and a lack of antiglycation activity. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is an important global clinical issue, requiring not only prevention but also effective treatment. Following TBI, diverse parallel and intertwined pathological mechanisms affecting biochemical, neurochemical, and inflammatory pathways can have a severe impact on the patient’s quality of life. The current review summarizes the evidence for the utility of amantadine in TBI in connection to its mechanism of action. Amantadine, the drug combining multiple mechanisms of action, may offer both neuroprotective and neuroactivating effects in TBI patients. Indeed, the use of amantadine in TBI has been encouraged by several clinical practice guidelines/recommendations. Amantadine is also available as an infusion, which may be of particular benefit in unconscious patients with TBI due to immediate delivery to the central nervous system and the possibility of precise dosing. In other situations, orally administered amantadine may be used. There are several questions that remain to be addressed: can amantadine be effective in disorders of consciousness requiring long-term treatment and in combination with drugs approved for the treatment of TBI? Do the observed beneficial effects of amantadine extend to disorders of consciousness due to factors other than TBI? Well-controlled clinical studies are warranted to ultimately confirm its utility in the TBI and provide answers to these questions.

This study aimed to evaluate the therapeutic potential of amantadine in a vincristine-induced peripheral neuropathy model in rats. Forty-eight male Wistar rats were used. The treated groups received oral amantadine at doses of 2, 5, 12, 25 and 50 mg/kg, with daily applications for 14 days. The mechanical paw withdrawal threshold was measured using a digital analgesimeter. Immunohistochemical analysis of IL-6, TNFα, MIP1α, IL-10, CX3CR1, CXCR4, SOD, CAT and GPx, and enzymatic activity analysis of CAT, SOD and GPx were performed, in addition to quantitative PCR of Grp78, Chop, Ho1, Perk, Bax, Bcl-xL, Casp 3, Casp 9, IL-6, IL-10, IL-18 and IL-1β. The results showed an increase in nociceptive thresholds in animals that received 25 mg/kg and 50 mg/kg amantadine. Immunohistochemistry showed a decrease in the immunostaining of IL-6, TNFα, MIP1α and CX3CR1, and an increase in IL-10. CAT and SOD showed an increase in both immunochemistry and enzymatic analysis. qPCR revealed a reduced expression of genes related to endoplasmic reticulum stress and regulation in the expression of immunological and apoptotic markers. Amantadine demonstrated antinociceptive, anti-inflammatory and antioxidant effects in the vincristine-induced peripheral neuropathy model in rats, suggesting that amantadine may be considered an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.

Abstract Background Persisting coma is a common complication in (neuro)intensive care in neurological disease such as acute ischemic stroke, intracerebral hemorrhage or subarachnoid hemorrhage. Amantadine acts as a nicotinic receptor antagonist, dopamine receptor agonist and non-competitive N-Methyl-D-aspartate receptor antagonist. Amantadine is a long-known drug, originally approved for treatment of influenza A and Parkinson`s Disease. It has been proven effective in improving vigilance after traumatic brain injury. The underlying mechanisms remain largely unknown, albeit anti-glutamatergic and dopaminergic effects might be most relevant. With limited evidence of amantadine efficacy in non-traumatic pathologies, the aim of our study is to assess the effects of amantadine for neuroenhancement in non-traumatic neurointensive patients with persisting coma. Methods An investigator-initiated, monocenter, phase IIb proof of concept open-label pilot study will be carried out. Based on the Simon design, 43 adult (neuro)intensive care patients who meet the clinical criteria of persisting coma not otherwise explained and

The usual adverse events of amantadine are dizziness, dry mouth, and peripheral edema. Postmarketing experience has revealed abnormal movements such as tremors, involuntary muscle contractions, and gait abnormalities. Herein, we report a case of an elderly male who presented with generalized twitching associated with amantadine. A 64-year-old male presenting with jerking movements within one day of onset was admitted. Sudden and involuntary distal lower and upper limb muscle twitching was observed. The subject presented subsequent brief movements when attempting to stand or hold arms antigravity. He was diagnosed with Parkinson’s disease three years ago. Eight days before the presentation to the emergency department, he consulted with his primary care physician, who prescribed amantadine to improve his motor symptoms. On the seventh day, he developed brisk abnormal movements. Laboratory exams, neuroimaging, and electroencephalogram were unremarkable. Amantadine was discontinued. After three days, the patient reported that his jerking movements had fully recovered. To the authors’ knowledge, 22 individuals with amantadine-associated myoclonus had already been reported in the literature. The pathophysiology of amantadine-induced myoclonus is probably related to serotoninergic pathways. Myoclonus secondary to amantadine was slightly more common in men. The population affected was elderly, with a mean and median age of 67.7 and 64 years.

Objective Amantadine has both anti-glutamatergic and dopaminergic action and may improve restless legs syndrome (RLS). We compared the efficacy and adverse-effect profile of amantadine and ropinirole in RLS.

This review summarized and analyzed the immunoassay techniques, such as enzyme-linked immunosorbent assay, immunochromatographic assay, and chemiluminescence immunoassay, which have been applied in the detection of amantadine residue, and provides an outlook on their development.

Introduction: TBIs contribute in over one-third of injury-related deaths with mortality rates as high as 50% in trauma centers serving the most severe TBI. The effect of TBI on mortality is about 10% across all ages. Amantadine hydrochloride is one of the most commonly prescribed medications for patients undergoing inpatient neurorehabilitation who have disorders of consciousness.6 It is a dopamine (DA) receptor agonist and a N-Methyl-D-aspartate (NMDA) receptor antagonist via dopamine release and dopamine reuptake inhibition. The current study will synthesize the current available evidence and show the effect of Amantadine in functional improvement after TBI. Research question: Does Amantadine have an effect on functional improvement of TBI patients? Material and methods: This systematic review included all randomized placebo-controlled trials that compare the use of Amantadine versus placebo for functional improvement of patients after TBI. Outcome measures included DRS, GCS and/or GOS scores. Results: Three studies with a total of 281 patients were included in the quantitative analyses. GRADE assessments show that there was a high certainty of evidence for functional improvement in terms of DRS scores. Discussion and conclusion: Evidence of this review show that the use of Amantadine may have a beneficial effect on functional outcome in moderate to severe traumatic brain injuries among adult patients. Given the still-limited body of knowledge, more relevant studies must be made exploring the impact of Amantadine therapies on promoting functional recovery within the brain injury rehabilitation care continuum, with the goals of achieving larger sample sizes and establishing the early- or later-treatment beneficial effects.

Purpose: To describe a case of bilateral interface fluid formation 2 years after laser-assisted in situ keratomileusis (LASIK) surgery caused by the side effect of amantadine. Observations: A 47-year-old male patient with a history of Parkinson's disease treated with amantadine who had uneventful LASIK surgery in both eyes 2 years ago, presented with a decline in vision over the past 6 weeks. Results: Best corrected vision was 20/200 and 20/400 in the right and left eye respectively. Intraocular pressures were measured within the normal range. Biomicroscopic exam showed bilateral corneal edema. Anterior segment optical coherence tomography (AS-OCT) revealed fluid accumulation within the LASIK flap interface in both corneas. The patient's corneal edema and fluid in the interface began to gradually resolve, and vision improved 2 weeks after discontinuing amantadine. Conclusions and Importance: Although there is no previous report, it is possible that amantadine may cause interface fluid formation in patients with LASIK surgery.

Purpose: To present a case of irreversible corneal edema after 10 years of amantadine use. A literature review was carried out to describe the clinical characteristics and outcomes of amantadine-induced corneal edema. Observations: A 36-year-old woman presented with a 6-week history of gradually progressive bilateral painless visual loss with visual acuity (VA) of 20/350 and 20/300 in the right and left eye, respectively. Examination showed bilateral diffuse central corneal edema with multiple Descemet membrane folds without endothelial guttata, keratic precipitates or intraocular inflammation. This did not respond to hypertonic saline drops and empirical treatment for presumed herpetic endotheliitis with oral acyclovir. Medication review revealed the use of amantadine 100mg daily for the past 10 years, prescribed by her neurologist for fatigue. Despite discontinuing amantadine, corneal edema was irreversible due to a markedly reduced endothelial cell count of 625 (right) and 680 cells/mm2 (left). Conclusions and Importance: This case highlights the need to consider amantadine as a cause of unexplained bilateral non-guttae corneal edema. A literature review of 33 case reports revealed broadly similar features of amantadine-induced corneal edema; whilst most cases had favorable outcomes with median VA 20/25 (interquartile range IQR 20/20–20/30) and complete resolution of corneal edema within 30 days (IQR 14–35) of amantadine discontinuation, most experienced low endothelial cell density 759 cells/mm2 (IQR 621–1078). Taken together, screening specular microscopy ought to be considered for those in whom amantadine is likely required long-term.

Metabolic profiling offers huge potential to highlight markers and mechanisms in support of toxicology and pathology investigations during drug development. The main objective was to modify therapy with adamantane derivatives: amantadine and rimantadine, to increase their bioavailability and evaluate the influence of such therapy on drug metabolism using Saccharomyces cerevisiae as the model organism. In this study, the profile of endogenous metabolites of a model organism was measured and interpreted to provide an opportunity to investigate changes induced by treatment with amantadine and rimantadine. It was found that resveratrol supplementation synergistically enhanced the effects of amantadine treatment and increased rimantadine metabolism, potentially reducing side effects. The fingerprinting strategy was used as an efficient technique for qualitatively evaluating and monitoring changes in the profiles of endogenous components and their contents in a model organism. Chemometric tools were employed to find marker compounds that can be defined as characteristic indicators of a pharmacological response to a therapeutic intervention. An improved understanding of the mechanisms involved in drug effect and an increased ability to predict individual variations in the drug response of organisms will improve the treatment process and the development of new therapies. [ABSTRACT FROM AUTHOR]

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A convenient method has been proposed for the preparation of new derivatives of adamantine-based drugs, such as memantine and rimantadine. The synthesis was performed by functionalization of amino-group of memantine and rimantadine by ipso-substitution of cyano-group at C5 position of 1,2,4-triazine scaffold with the corresponding aminoadamantane moieties with subsequent aza-Diels–Alder transformation of 1,2,4-triazine cycle into pyridine one in some cases. [ABSTRACT FROM AUTHOR]