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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]

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]

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]

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]

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]

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]

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.

BACKGROUND: There are several well-known treatments for Restless Legs Syndrome (RLS), including dopamine agonists (pramipexole, ropinirole, rotigotine), anticonvulsants (gabapentin and its analogs, pregabalin), oral or intravenous iron, opioids and benzodiazepines. However, in clinical practice, treatment is sometimes limited due to incomplete response or side effects and it is necessary to be aware of other treatment options for RLS, which is the purpose of this review. METHODS: We performed a narrative review detailing all of the lesser known pharmacological treatment literature on RLS. The review purposefully excludes well-established, well-known treatments for RLS which are widely accepted as treatments for RLS in evidence-based reviews. We also have emphasized the pathogenetic implications for RLS of the successful use of these lesser known agents. RESULTS: Alternative pharmacological agents include clonidine which reduces adrenergic transmission, adenosinergic agents such as dipyridamole, glutamate AMPA receptor blocking agents such as perampanel, glutamate NMDA receptor blocking agents such as amantadine and ketamine, various anticonvulsants (carbamazepine/oxcarbazepine, lamotrigine, topiramate, valproic acid, levetiracetam), anti-inflammatory agents such as steroids, as well as cannabis. Bupropion is also a good choice for the treatment of co-existent depression in RLS because of its pro-dopaminergic properties. DISCUSSION: Clinicians should first follow evidence-based review recommendations for the treatment of RLS but when the clinical response is either incomplete or side effects are intolerable other options can be considered. We neither recommend nor discourage the use of these options, but leave it up to the clinician to make their own choices based upon the benefit and side effect profiles of each medication.

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]

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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

The prevalence of dry eye syndrome (DES) in Parkinson's disease (PD) reaches 87% and leads to impaired quality of life in many patients.Objective: to evaluate the lacrimal function and the effect of dopaminergic therapy in patients with PD.Material and methods: 43 patients with stage II–III PD according to Hoehn and Yahr (H&Y) receiving therapy with levodopa (n=17), amantadines (n=13) and dopamine receptor agonists (ADR) (n=28) were assessed using Schirmer's test (to estimate tear flow), sialometry, Unified Parkinson's Disease Rating Scale (UPDRSI-IV), Schwab and England Activities of Daily Living scale (Sch&En), the Parkinson’s Disease Questionnaire Summary Index (PDQ-39), the Mini Mental State Examination Scale (MMSE), the Non-Motor Symptom Questionnaire (NMSQ), the American Urological Association Symptom Scale (AUA), the Gastrointestinal Symptom Rating Scale (GSRS), the Bristol Stool Form Scale (BSFS).Results. Lacrimal insufficiency was found in 49% of patients. It occurred more frequently (χ2=9.546; p=0.003) in patients taking amantadine and correlated with the daily dose of amantadine (r-S=-0.359). It did not depend on the intake of ADR and levodopa and their doses but correlated with the UPDRS-IV score (r-S= -0.463), namely with the presence and duration of OFF-periods. Lacrimal insufficiency correlated with the Sch&En score (r-S=0.321) and non-motor parameters: UPDRSI (r-S =-0.302), NMSQ (r-S=-0.435), constipation domain of the GSRS (r-S=-0.362), BSFS (r-S=0.363). It was not related to age, gender, stage and duration of PD, motor symptoms of parkinsonism (assessed during the ON-phase) and was not related to salivation (although it was reduced in 39.5% of patients).Conclusion. Lacrimal insufficiency is observed in half of patients with stage II–III PD; it is related to the presence and duration of OFF-periods, the severity of other autonomic disorders and the use of amantadines, suggesting the role of dopamine dysregulation, neurodegeneration of autonomic centers and anticholinergic therapy in the development of DES in PD.

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]

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]

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]