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Archives of Medical Research Oct 2020
Topics: Amantadine; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Pandemics; Parkinsonian Disorders; Pneumonia, Viral; SARS-CoV-2
PubMed: 32723524
DOI: 10.1016/j.arcmed.2020.07.002 -
Journal of Neural Transmission (Vienna,... Sep 2022The trajectory of the use of dopamine replacement therapy (DRT) in Parkinson's disease (PD) is variable and doses may need to be increased, but also tapered. The plan... (Review)
Review
The trajectory of the use of dopamine replacement therapy (DRT) in Parkinson's disease (PD) is variable and doses may need to be increased, but also tapered. The plan for dose adjustment is usually done as per drug information recommendations from the licensing bodies, but there are no clear guidelines with regards to the best practice regarding the tapering off schedule given sudden dose reductions of drugs such as dopamine agonists may have serious adverse consequences. A systematic literature search was, therefore, performed to derive recommendations and the data show that there are no controlled studies or evidence-based recommendations how to taper or discontinue PD medication in a systematic manner. Most of the data were available on the dopamine agonist withdrawal syndrome (DAWS) and we found only two instructions on how to reduce pramipexole and rotigotine published by the EMA. We suggest that based on the available data, levodopa, dopamine agonists (DA), and amantadine should not be discontinued abruptly. Abrupt or sudden reduction of DA or amantadine in particular can lead to severe life-threatening withdrawal symptoms. Tapering off levodopa, COMT inhibitors, and MAO-B inhibitors may worsen motor and non-motor symptoms. Based on our clinical experience, we have proposed how to reduce PD medication and this work will form the basis of a future Delphi panel to define the recommendations in a consensus.
Topics: Amantadine; Dopamine; Dopamine Agonists; Humans; Levodopa; Parkinson Disease; Substance Withdrawal Syndrome
PubMed: 34324057
DOI: 10.1007/s00702-021-02389-x -
Archives of Medical Research Oct 2020
Topics: Amantadine; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Pandemics; Parkinsonian Disorders; Pneumonia, Viral; SARS-CoV-2
PubMed: 32660794
DOI: 10.1016/j.arcmed.2020.07.001 -
Revista Brasileira de Psiquiatria (Sao... 2018Amantadine blocks N-methyl-D-aspartate (NMDA) receptors and has dopaminergic and noradrenergic action, a neurochemical profile that suggests its potential as an... (Review)
Review
OBJECTIVE
Amantadine blocks N-methyl-D-aspartate (NMDA) receptors and has dopaminergic and noradrenergic action, a neurochemical profile that suggests its potential as an antidepressant drug. We conducted a systematic review of preclinical and clinical studies addressing the effects of amantadine in animal models of depression and in patients with depression.
METHODS
PubMed, Science Direct, and Web of Science were searched up to September 1, 2017 to identify clinical and preclinical studies. The following search terms were used: "amantadine AND depress*"; "amantadine AND mood"; "amantadine AND animal models AND antidepres*"; and "amantadine AND (forced swim, learned helplessness, reserpine, chronic mild stress, anhedonia, sucrose preference)."
RESULTS
Amantadine had antidepressant-like effects in animal models and appeared to potentiate the antidepressant effects of other antidepressants. These preclinical findings have received some support from the results of small open-label clinical trials, suggesting that amantadine can reduce depressive symptomatology and potentiate the antidepressant effects of monoaminergic drugs. In addition to its glutamatergic and dopaminergic effects, the potential antidepressant-like effects of amantadine have been linked to molecular and cellular actions, such as increased expression of neurotrophic factors (e.g., brain-derived neurotrophic factor), activation of σ1 receptors, decreased corticosterone levels, and decreased inflammatory response to stress.
CONCLUSION
Amantadine is an interesting candidate as new antidepressant drug for the treatment of depression.
Topics: Amantadine; Animals; Antidepressive Agents; Biogenic Monoamines; Clinical Trials as Topic; Depressive Disorder; Disease Models, Animal; Drug Evaluation, Preclinical; Humans
PubMed: 29898194
DOI: 10.1590/1516-4446-2017-2393 -
Psychopharmacology Bulletin Feb 2023Memenatine is USFDA approved for dementia of Alzheimer's disease. Apart from this indication, trend of its use in psychiatry is on the rise addressing a multitude of... (Review)
Review
BACKGROUND
Memenatine is USFDA approved for dementia of Alzheimer's disease. Apart from this indication, trend of its use in psychiatry is on the rise addressing a multitude of disorders.
STUDY QUESTION
Memantine remains one of only few psychotropic drugs with antiglutamate activity. This might impart it a therapeutic potential in treatment-resistant major psychiatric disorders characterized by neuroprogression. We reviewed memantine basic pharmacology and its diversifying clinical indications while examining the extant evidence.
METHODS
EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane Database of Systemic Reviews were searched for all relevant studies up to date of November, 2022.
RESULTS
Sound evidence supports use of memantine for major neuro-cognitive disorder due to Alzheimer's disease and severe vascular dementia, obsessive-compulsive disorder, treatment-resistant schizophrenia, and, ADHD. Modicum evidence supports use of memantine for PTSD, GAD and pathological gambling. Less compelling evidence is present for use in catatonia. No evidence supports use for core symptoms of autism spectrum disorder.
CONCLUSIONS
Memantine is an important addition to the psychopharmacological armamentarium. Level of evidence supporting the use of memantine in these off-label indications is highly variable, and hence, sound clinical judgment is necessary for its proper use and placement in real-life psychiatric practice and psychopharmacotherapy algorithms.
Topics: Humans; Memantine; Alzheimer Disease; Autism Spectrum Disorder; Psychiatry; Off-Label Use
PubMed: 36873917
DOI: No ID Found -
Current Neuropharmacology 2016Glutamatergic neurotransmission, of special importance in the human brain, is implicated in key brain functions such as synaptic plasticity and memory. The excessive... (Review)
Review
Glutamatergic neurotransmission, of special importance in the human brain, is implicated in key brain functions such as synaptic plasticity and memory. The excessive activation of N-methyl- D-aspartate (NMDA) receptors may result in excitotoxic neuronal damage; this process has been implicated in the pathomechanism of different neurodegenerative disorders, such as Alzheimer's disease (AD). Memantine is an uncompetitive antagonist of NMDA receptors with a favorable pharmacokinetic profile, and is therefore clinically well tolerated. Memantine is approved for the treatment of AD, but may additionally be beneficial for other dementia forms and pain conditions. Kynurenic acid (KYNA) is an endogenous antagonist of NMDA receptors which has been demonstrated under experimental conditions to be neuroprotective. The development of a well-tolerated NMDA antagonist may offer a novel therapeutic option for the treatment of neurodegenerative disease and pain syndromes. KYNA may be a valuable candidate for future drug development.
Topics: Alzheimer Disease; Animals; Brain; Excitatory Amino Acid Antagonists; Humans; Kynurenic Acid; Memantine; Receptors, N-Methyl-D-Aspartate; Synapses
PubMed: 26564141
DOI: 10.2174/1570159x14666151113123221 -
Neuropharmacology Feb 2024The great potential for NMDA receptor modulators as druggable targets in neurodegenerative disorders has been met with limited success. Considered one of the rare... (Review)
Review
The great potential for NMDA receptor modulators as druggable targets in neurodegenerative disorders has been met with limited success. Considered one of the rare exceptions, memantine has consistently demonstrated restorative and prophylactic properties in many AD models. In clinical trials memantine slows the decline in cognitive performance associated with AD. Here, we provide an overview of the basic properties including pharmacological targets, toxicology and cellular effects of memantine. Evidence demonstrating reductions in molecular, physiological and behavioural indices of AD-like impairments associated with memantine treatment are also discussed. This represents both an extension and homage to Dr. Chris Parson's considerable contributions to our fundamental understanding of a success story in the AD treatment landscape.
Topics: Humans; Memantine; Alzheimer Disease; Receptors, N-Methyl-D-Aspartate; Cognition
PubMed: 37832633
DOI: 10.1016/j.neuropharm.2023.109737 -
BMC Complementary and Alternative... Aug 2015Multi-factorial etiology exists in pathophysiology of neurodegenerative diseases. The imbalance of anti-oxidant enzymes and dopamine level leads to Parkinsonism. The...
BACKGROUND
Multi-factorial etiology exists in pathophysiology of neurodegenerative diseases. The imbalance of anti-oxidant enzymes and dopamine level leads to Parkinsonism. The objective of this study was to assess the protective effect of Spirulina fusiform alone and in combination with amantadine against Parkinsonism effect in 6-hydroxydopamine (6-OHDA) induced rat model.
METHODS
S. fusiform was administered in different groups (500 mg/kg, once daily and twice daily) and a combination of spirulina (500 mg/kg, once daily) with amantadine (20 mg/kg once daily) for 30 days before and 14 days after a single injection of 6-OHDA into the dorsal striatum. Post lesion produced rotational behavior which was measured at two week intervals (37th and 44th day). Locomotors activity was also done at 44th and muscle coordination at 48th day. Dorsal striatum was isolated from rat brain for evaluating the antioxidant assays and dopamine content at 49th day.
RESULTS
Both the body rotations (ipsilateral and contralateral) were found to have a statistically significant (p<0.001) decrease by 34.26 and 52% after treatment with spirulina (Twice a day) in spirulina treated lesioned group. A higher percentage of improvement was shown in the reduction of ipsilateral (57.34%) and contralateral (78.3%) rotations in combination of spirulina with amantadine treated lesioned group rather than spirulina alone treated lesioned groups when compared with positive control lesioned group. Body movements and locomotor activity were improved statistically (p<0.0001) significant in both treated lesioned groups (Combination of spirulina with amantadine and spirulina twice daily). Similar results were also seen in anti-oxidant levels which later on reached to the normal value. The levels of dopamine content had a statistically significant (p<0.0001) increase by 78.3% only in case of spirulina with amantadine treated lesioned group.
CONCLUSION
Spirulina is a potent nutraceutical supplement all over the world, so my preclinical study may contribute to give an additional adjuvant drug therapy in aging related disorders (Neurodegenerative as well as diabetes associated neurodegenerative disorders).
Topics: Amantadine; Animals; Dietary Supplements; Neuroprotective Agents; Oxidopamine; Parkinsonian Disorders; Rats; Spirulina
PubMed: 26306668
DOI: 10.1186/s12906-015-0815-0 -
Journal of Molecular Medicine (Berlin,... Mar 2021Memantine is used in Alzheimer's disease treatment as a non-competitive modern-affinity strong voltage-dependent N-methyl-D-aspartate receptor antagonist. The... (Review)
Review
Memantine is used in Alzheimer's disease treatment as a non-competitive modern-affinity strong voltage-dependent N-methyl-D-aspartate receptor antagonist. The fundamental role of these receptors is to bind glutamate: the main excitatory neurotransmitter in the brain, believed to play a crucial role in neuronal plasticity and learning mechanisms. Glutamate transmission plays an important role in all internal CNS structures and maintains the physiological state of the brain. Excessive glutamate transmission can lead to enlarged calcium ion current which may cause neurotoxicity; however, insufficient transmission can drastically alter the information flow in neurons and the brain, potentially causing schizophrenia-like symptoms by replacing lost information with completely new stimuli. Hence, it is possible that the modulation of NMDA activity may give rise to pathophysiological states. Available literature and clinical trials indicate that memantine is well tolerated by patients, with very few and light side effects. There is a belief that memantine may also benefit other conditions such as schizophrenia and depression.
Topics: Alzheimer Disease; Antidepressive Agents; Antipsychotic Agents; Clinical Trials as Topic; Depression; Drug Repositioning; Excitatory Amino Acid Antagonists; Glutamic Acid; Humans; Memantine; N-Methylaspartate; Neuronal Plasticity; Receptors, N-Methyl-D-Aspartate; Schizophrenia; Serotonin 5-HT3 Receptor Antagonists
PubMed: 33447926
DOI: 10.1007/s00109-020-01982-z -
International Journal of Molecular... Apr 2022Along with the increase in life expectancy in the populations of developed and developing countries resulting from better access and improved health care, the number of... (Review)
Review
Along with the increase in life expectancy in the populations of developed and developing countries resulting from better access and improved health care, the number of patients with dementia, including Alzheimer's disease (AD), is growing. The disease was first diagnosed and described at the beginning of the 20th century. However, to this day, there is no effective causal therapy, and symptomatic treatment often improves patients' quality of life only for a short time. The current pharmacological therapies are based mainly on the oldest hypotheses of the disease-cholinergic (drugs affecting the cholinergic system are available), the hypothesis of amyloid-β aggregation (an anti-amyloid drug was conditionally approved by the FDA in 2020), and one drug is an N-methyl-D-aspartate receptor (NMDAR) antagonist (memantine). Hypotheses about AD pathogenesis focus on the nervous system and the brain. As research progresses, it has become known that AD can be caused by diseases that have been experienced over the course of a lifetime, which could also affect other organs. In this review, we focus on the potential association of AD with the digestive system, primarily the gut microbiota. The role of diet quality in preventing and alleviating Alzheimer's disease is also discussed. The problem of neuroinflammation, which may be the result of microbiota disorders, is also described. An important aspect of the work is the chapter on the treatment strategies for changing the microbiota, potentially protecting against the disease and alleviating its course in the initial stages.
Topics: Alzheimer Disease; Brain-Gut Axis; Cholinergic Agents; Humans; Memantine; Microbiota; Quality of Life; Receptors, N-Methyl-D-Aspartate
PubMed: 35563253
DOI: 10.3390/ijms23094862