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Journal of Neural Transmission (Vienna,... Feb 2021The aim of the current review was to provide a new, in-depth insight into possible pharmacological targets of amantadine to pave the way to extending its therapeutic use... (Review)
Review
The aim of the current review was to provide a new, in-depth insight into possible pharmacological targets of amantadine to pave the way to extending its therapeutic use to further indications beyond Parkinson's disease symptoms and viral infections. Considering amantadine's affinities in vitro and the expected concentration at targets at therapeutic doses in humans, the following primary targets seem to be most plausible: aromatic amino acids decarboxylase, glial-cell derived neurotrophic factor, sigma-1 receptors, phosphodiesterases, and nicotinic receptors. Further three targets could play a role to a lesser extent: NMDA receptors, 5-HT3 receptors, and potassium channels. Based on published clinical studies, traumatic brain injury, fatigue [e.g., in multiple sclerosis (MS)], and chorea in Huntington's disease should be regarded potential, encouraging indications. Preclinical investigations suggest amantadine's therapeutic potential in several further indications such as: depression, recovery after spinal cord injury, neuroprotection in MS, and cutaneous pain. Query in the database http://www.clinicaltrials.gov reveals research interest in several further indications: cancer, autism, cocaine abuse, MS, diabetes, attention deficit-hyperactivity disorder, obesity, and schizophrenia.
Topics: Amantadine; Diamond; Humans; Huntington Disease; Parkinson Disease; Receptors, N-Methyl-D-Aspartate
PubMed: 33624170
DOI: 10.1007/s00702-021-02306-2 -
Advances in Clinical and Experimental... Oct 2021Ischemia-reperfusion models are used to evaluate treatment options that may minimize cellular damage after ischemia.
BACKGROUND
Ischemia-reperfusion models are used to evaluate treatment options that may minimize cellular damage after ischemia.
OBJECTIVES
To investigate the effects of amantadine and topiramate on apoptosis and cellular oxidative damage.
MATERIAL AND METHODS
This experiment was performed using 30 male Wistar albino rats. The right internal carotid artery was identified and clamped with an aneurysm clip under general anesthesia, except for animals in the control group. After 10 min of occlusion, the aneurysm clip was removed, allowing reperfusion. After reperfusion and a waiting period of 12 h, the test and control groups were intraperitoneally administered the following solutions: the sham group received 10 mg/kg of isotonic solution, the amantadine group received 20 mg/kg of amantadine, the topiramate group received 40 mg/kg of topiramate, and the amantadine-topiramate group received 20 mg/kg of amantadine and 40 mg/kg of topiramate. After 24 h, the rats were euthanized.
RESULTS
Apoptosis was evaluated using the TUNEL method. Total antioxidant status (TAS), total oxidant status (TOS), total thiol, and ischemia-modified albumin (IMA) levels were measured in both brain tissue and serum samples. The rate of apoptosis in the sham and amantadine groups increased significantly compared to the control group and the non-ischemic counter hemisphere. In the amantadine-topiramate group, both serum TAS and tissue thiol levels decreased. Tissue TOS levels were significantly higher in the topiramate group compared to all other test groups. Tissue TAS levels were significantly higher in the amantadine group compared to all other test groups.
CONCLUSIONS
This experimental ischemia-reperfusion model revealed that topiramate reduces apoptosis in the early period after ischemia and that its combination with amantadine does not provide additional benefits against cell death. However, topiramate did not have an inhibitory effect on the oxidative stress biomarkers used in our study (TAS, TOS, IMA, and thiol). Studies that reveal the neuroprotective mechanism of action and long-term effects of topiramate are needed to complement this study.
Topics: Amantadine; Animals; Antioxidants; Biomarkers; Brain Ischemia; Male; Oxidative Stress; Rats; Rats, Wistar; Reperfusion; Reperfusion Injury; Serum Albumin; Topiramate
PubMed: 34510842
DOI: 10.17219/acem/138327 -
The Cochrane Database of Systematic... Mar 2013Influenza is a communicable acute respiratory infection which, during epidemics, can cause high morbidity and mortality rates. Traditional Chinese medicinal herbs, often... (Review)
Review
BACKGROUND
Influenza is a communicable acute respiratory infection which, during epidemics, can cause high morbidity and mortality rates. Traditional Chinese medicinal herbs, often administered following a particular Chinese medical theory, may be a potential treatment of choice.
OBJECTIVES
To assess the effect of Chinese medicinal herbs used to prevent and treat influenza and to estimate the frequency of adverse effects.
SEARCH METHODS
We searched CENTRAL (2012, Issue 11), MEDLINE (January 1966 to November week 2, 2012), EMBASE (January 1988 to November 2012) and CNKI (January 1988 to 29 March 2012). We also searched reference lists of articles and the WHO ICTRP search portal (November 2012).
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing traditional Chinese medicinal herbs with placebo, no treatment or conventional medicine normally used in preventing and treating uncomplicated influenza.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed trial quality.
MAIN RESULTS
We included 18 studies involving 2521 participants. The methodological quality of 17 included studies was poor. Included RCTs separately compared medicinal herbs with different antiviral drugs, precluding any pooling of results. Only three indicated that compared with antiviral drugs, Chinese medicinal herbs may be effective in preventing influenza and alleviating influenza symptoms. 'Ganmao' capsules were found to be more effective than amantadine in decreasing influenza symptoms and speeding recovery in one study (in which adverse reactions were mentioned in the amantadine group although no data were reported). There were no significant differences between 'E Shu You' and ribavirin in treating influenza, nor in the occurrence of adverse reactions. Ten studies reported mild adverse reactions.
AUTHORS' CONCLUSIONS
Most Chinese medical herbs in the included studies showed similar effects to antiviral drugs in preventing or treating influenza. Few were shown to be superior to antiviral drugs. No obvious adverse events were reported in the included studies. However, current evidence remains weak due to methodological limitations of the trials. More high-quality RCTs with larger numbers of participants and clear reporting are needed.
Topics: Amantadine; Antiviral Agents; Drugs, Chinese Herbal; Humans; Influenza, Human; Phytotherapy; Randomized Controlled Trials as Topic; Ribavirin
PubMed: 23543533
DOI: 10.1002/14651858.CD004559.pub4 -
International Journal of Molecular... Jul 2022Patients with Parkinson’s disease are prone to a higher incidence of melanoma. Amantadine (an anti-Parkinson drug) possesses the antiproliferative potential that can...
Patients with Parkinson’s disease are prone to a higher incidence of melanoma. Amantadine (an anti-Parkinson drug) possesses the antiproliferative potential that can be favorable when combined with other chemotherapeutics. Cisplatin (CDDP) and mitoxantrone (MTO) are drugs used in melanoma chemotherapy, but they have many side effects. (1) Clinical observations revealed a high incidence of malignant melanoma in patients with Parkinson’s disease. Amantadine as an anti-Parkinson drug alleviates symptoms of Parkinson’s disease and theoretically, it should have anti-melanoma properties. (2) To characterize the interaction profile for combinations of amantadine with CDDP and MTO in four human melanoma cell lines (A375, SK-MEL 28, FM55P and FM55M2), type I isobolographic analysis was used in the MTT test. (3) Amantadine produces the anti-proliferative effects in various melanoma cell lines. Flow cytometry analysis indicated that amantadine induced apoptosis and G1/S phase cell cycle arrest. Western blotting analysis showed that amantadine markedly decreased cyclin-D1 protein levels and increased p21 levels. Additionally, amantadine significantly increased the Bax/Bcl-2 ratio. The combined application of amantadine with CDDP at the fixed-ratio of 1:1 exerted an additive interaction in the four studied cell lines in the MTT test. In contrast, the combination of amantadine with MTO (ratio of 1:1) produced synergistic interaction in the FM55M2 cell line in the MTT (* p < 0.05). The combination of amantadine with MTO was also additive in the remaining tested cell lines (A375, FM55P and SK-MEL28) in the MTT test. (4) Amantadine combined with MTO exerted the most desirable synergistic interaction, as assessed isobolographically. Additionally, the exposure of melanoma cell lines to amantadine in combination with CDDP or MTO augmented the induction of apoptosis mediated by amantadine alone.
Topics: Amantadine; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cisplatin; Cytostatic Agents; Humans; Melanoma; Parkinson Disease
PubMed: 35886997
DOI: 10.3390/ijms23147653 -
Contemporary Clinical Trials May 2022COVID-19, a disease caused by infection with the SARS-CoV-2 virus, is asymptomatic or mildly symptomatic in most cases. Some patients, usually burdened with risk factors...
The use of amantadine in the prevention of progression and treatment of COVID-19 symptoms in patients infected with the SARS-CoV-2 virus (COV-PREVENT): Study rationale and design.
BACKGROUND
COVID-19, a disease caused by infection with the SARS-CoV-2 virus, is asymptomatic or mildly symptomatic in most cases. Some patients, usually burdened with risk factors develop acute respiratory failure and other organ dysfunction. In such cases, the mortality rate is very high despite the use of intensive therapy. Amantadine has complex activity including antiviral, antiinflammatory and dopaminergic effects. This clinical trial will assess the efficacy and safety of amantadine in the prevention of COVID-19 progression toward acute respiratory failure and neurological complications.
METHODS AND RESULTS
The trial will enroll 200 patients who are positive for SARS-CoV-2 infection and have one or more risk factors for worsening the disease. These patients will be included as hospitalized or ambulatory subjects for early treatment of illness. The recruitment will take place in 8 centers covering different regions of Poland. For 14 days they will be given either 200 mg of amantadine a day or placebo. Our hypothesis is a considerable reduction in the number of patients with progression toward respiratory insufficiency or neurological complications thanks to the treatment of amantadine.
CONCLUSIONS
Demonstrating the efficacy and safety of amantadine treatment in improving the clinical condition of patients diagnosed with COVID-19 is of great importance in combating the effects of the pandemic. It has potential to influence on the severity and course of neurological complications, which are very common and persist long after the infection as long-COVID syndrome.
CLINICAL TRIAL REGISTRATION
www.
CLINICALTRIALS
gov identification no. NCT04854759; Eudra CT number: 2021-001144-98 (dated 27 February 2021).
Topics: Amantadine; COVID-19; Humans; Respiratory Insufficiency; SARS-CoV-2; Treatment Outcome; Post-Acute COVID-19 Syndrome; COVID-19 Drug Treatment
PubMed: 35390511
DOI: 10.1016/j.cct.2022.106755 -
Canadian Family Physician Medecin de... Mar 2008
Topics: Amantadine; Antiviral Agents; Humans; Influenza Vaccines; Influenza, Human; Mass Vaccination; Oseltamivir; Rimantadine; Zanamivir
PubMed: 18337537
DOI: No ID Found -
BMJ Open Jan 2024Fatigue is one of the most disabling symptoms of multiple sclerosis (MS), and effective treatments are lacking. Amantadine is one of the most used treatments, although...
Amantadine and/or transcranial magnetic stimulation for fatigue associated with multiple sclerosis (FETEM): study protocol for a phase 3 randomised, double-blind, cross-over, controlled clinical trial.
INTRODUCTION
Fatigue is one of the most disabling symptoms of multiple sclerosis (MS), and effective treatments are lacking. Amantadine is one of the most used treatments, although its efficacy is under debate. Transcranial magnetic stimulation (TMS) is a promising intervention that has shown positive effects in some preliminary investigations. We aim to investigate the effect of 6 weeks of amantadine and/or TMS in fatigue due to MS.
METHODS AND ANALYSIS
The study is a national, multicentre, phase 3, randomised, double-blind, cross-over, placebo-controlled and sham-controlled clinical trial. Adult patients with relapsing-remitting MS, Expanded Disability Status Scale score of 1.5-4.5 and Fatigue Severity Score>4 are eligible for the trial. Participants will be randomised to one of the sequences of the study. Each sequence consists of four periods of 6 weeks of treatment and three washout periods of 12-18 weeks. All patients will receive all the combinations of therapies. The primary outcome is the Modified Fatigue Impact Scale. The secondary outcomes are the Symbol Digit Modalities Test (cognition), Beck Depression Inventory-II (depressive symptoms) and Short-Survey 12 (quality of life). Safety and cost-effectiveness will also be evaluated. An exploratory substudy including MRI and blood biomarkers will be conducted.
ETHICS AND DISSEMINATION
The study is approved by the Ethics Committee of the Hospital Clinico San Carlos and the Spanish Agency of Medications and Medical Devices. All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences.
TRIAL REGISTRATION NUMBER
EudraCT 2021-004868-95; NCT05809414.
Topics: Adult; Humans; Multiple Sclerosis; Transcranial Magnetic Stimulation; Quality of Life; Amantadine; Double-Blind Method; Fatigue; Treatment Outcome; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Clinical Trials, Phase III as Topic
PubMed: 38176857
DOI: 10.1136/bmjopen-2023-078661 -
Canadian Respiratory Journal Oct 2003To evaluate the efficacy and safety of amantadine and rimantadine, the first generation antivirals, for the prophylaxis of influenza virus. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To evaluate the efficacy and safety of amantadine and rimantadine, the first generation antivirals, for the prophylaxis of influenza virus.
DATA SOURCES
A systematic search of the English language literature using MEDLINE, EMBASE, Current Contents and the Cochrane database from 1966 to April 2002, as well as a manual search of references from retrieved articles, were performed.
STUDY SELECTION
Prospective, randomized, controlled clinical trials evaluating amantadine and rimantadine for prophylaxis of naturally occurring influenza A illness were considered. The control arm used either a placebo or an antiviral agent.
DATA EXTRACTION
Each trial was assessed by two authors to determine the adequacy of randomization and description of withdrawals. Efficacy data were extracted according to a predefined protocol. Discrepancies in data extraction among the investigators were solved by consensus. Nine prophylaxis studies of amantadine and rimantadine met the criteria for this systematic review.
DATA SYNTHESIS
Seven amantadine versus placebo trials (n=1797), three rimantadine versus placebo trials (n=688) and two amantadine versus rimantadine studies (n=455) were included for the meta-analysis on the prevention of influenza A illness. The summary of results for the relative odds of illness indicated a 64% reduction in the amantadine group compared with placebo (OR 0.36, 95% CI 0.23 to 0.55, P< or =0.001), a 75% reduction in illness for the rimantadine group compared with placebo (OR 0.25, 95% CI 0.07 to 0.97, P=0.05) and no significant differences in the odds of illness for the amantadine versus rimantadine groups (OR 1.15, 95% CI 0.57 to 2.32, P=0.32). The summary of results examining adverse events showed significantly higher odds of central nervous system adverse reactions and premature withdrawal from the clinical trials in the amantadine-treated group than in the placebo-treated group. Compared with the placebo-treated group, the rimantadine-treated group did not have a significantly higher rate of withdrawal or central nervous system events. However, there was a significant increase in the odds of gastrointestinal adverse events for those treated with rimantadine compared with those treated with placebo (OR 3.34, 95% CI 1.17 to 9.55, P=0.03). In the comparative trials of amantadine to rimantadine, rimantadine was associated with an 82% reduction in the odds of central nervous system events (OR 0.18, 95% CI 0.03 to 1.00, P=0.05) and a 60% reduction in the odds of discontinuing treatment (OR 0.40, 95% CI 0.20 to 0.79, P=0.009).
CONCLUSION
This meta-analysis demonstrates that amantadine and rimantadine are superior to placebo in the prevention of influenza A illness. Both antiviral agents have an increased number of adverse events compared with placebo; however, the use of amantadine is associated with significantly higher numbers of central nervous system events and treatment withdrawals compared with rimantadine. Thus, rimantadine should be the preferred agent in this class for the prevention of influenza A virus infection and should be made available in Canada.
Topics: Amantadine; Antiviral Agents; Canada; Data Interpretation, Statistical; Drug Administration Schedule; Humans; Influenza A virus; Influenza, Human; Randomized Controlled Trials as Topic; Rimantadine
PubMed: 14571290
DOI: 10.1155/2003/453183 -
Journal of Viral Hepatitis Sep 2005Treatment of chronic hepatitis C (CHC) continues to be an important and growing challenge. As the response rate to FDA-approved treatment improved over the past decade,... (Review)
Review
Treatment of chronic hepatitis C (CHC) continues to be an important and growing challenge. As the response rate to FDA-approved treatment improved over the past decade, we are facing increasing number of difficult-to-treat patients such as those who have failed prior anti-viral therapy. The role of amantadine in the treatment of CHC remains unclear. Studies thus far have produced conflicting results, and type II error could not be excluded. This review summarized results published in the literature from 1997 to 2003, and reviewed the existing questions and controversies regarding the use of amantadine. Current literature suggests that amantadine is ineffective as monotherapy. Amantadine increased the sustained virologic response of certain treatment naïve patients when used in combination with interferon, and may be effective as an adjunct to interferon-based combination therapy in some patients who have failed or relapsed on prior therapy. Factors such as small sample size, patient characteristics, and differences in treatment protocols including amantadine preparation and duration of therapy might explain the conflicting observations of various studies. Further investigations are needed to define optimal dosing and formulation of amantadine, and its appropriate role in management of CHC infection.
Topics: Amantadine; Antiviral Agents; Hepatitis C, Chronic; Humans
PubMed: 16108758
DOI: 10.1111/j.1365-2893.2005.00622.x -
Biochimica Et Biophysica Acta Apr 2014Many viral genomes encode small, integral membrane proteins that form homo-oligomeric channels in membrane, and they transport protons, cations, and other molecules... (Review)
Review
Many viral genomes encode small, integral membrane proteins that form homo-oligomeric channels in membrane, and they transport protons, cations, and other molecules across the membrane barrier to aid various steps of viral entry and maturation. These viral proteins, collectively named viroporins, are crucial for viral pathogenicity. In the past five years, structures obtained by nuclear magnetic resonance (NMR), X-ray crystallography, and electron microscopy (EM) showed that viroporins often adopt minimalist architectures to achieve their functions. A number of small molecules have been identified to interfere with their channel activities and thereby inhibit viral infection, making viroporins potential drug targets for therapeutic intervention. The known architectures and inhibition mechanisms of viroporins differ significantly from each other, but some common principles are shared between them. This review article summarizes the recent developments in the structural investigation of viroporins and their inhibition by antiviral compounds. This article is part of a Special Issue entitled: Viral Membrane Proteins-Channels for Cellular Networking.
Topics: Amantadine; Antiviral Agents; Magnetic Resonance Spectroscopy; Viral Matrix Proteins
PubMed: 24055819
DOI: 10.1016/j.bbamem.2013.09.004