-
Romanian Journal of Morphology and... 2020Patients with serious mental illness are a high-risk category of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients with schizophrenia are... (Review)
Review
Patients with serious mental illness are a high-risk category of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients with schizophrenia are not participatory and have increased mortality and morbidity, patients with dementia cannot be cared for while depression, anxiety, bipolar tubing are associated with low immune status. Social stress is amplified by social isolation, amplifying depression and the mechanisms of decreased immunity. Hygiene measures and prophylactic behavior are impossible to put into practice in conditions of chronic mental illness. In coronavirus disease 2019 (COVID-19), the risk for severe development is associated with the presence of comorbidities and immune system deficiency. Prothrombotic status, cytokine storm and alveolar destruction are mechanisms that aggravate the evolution of patients, especially in the context in which they have dysfunction of the autonomic system. The activity of proinflammatory cytokines is accentuated by hyperglutamatergia, which potentiates oxidative stress and triggers the mechanisms of neural apoptosis by stimulating microglial activation. Activation of M1-type microglia has an important role in pathogenesis of major psychiatric disorders, such as major depression, schizophrenia or bipolar disorder, and may associate hippocampal atrophy and disconnection of cognitive structures. Memantine and Amantadine, N-methyl-D-aspartate (NMDA) glutamate receptor inhibitors, have demonstrated, through their pharmacological profile, psychotropic effects but also antiviral properties. In the conditions of the COVID-19 pandemic, based on these arguments, we suggest that they can be associated with the therapy with the basic psychotropics, Memantine or Amantadine, for the control of neuropsychiatric symptoms but also as adjuvants with antiviral action.
Topics: Amantadine; Antiparkinson Agents; COVID-19; Comorbidity; Humans; Memantine; Mental Disorders; Pandemics; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34171050
DOI: 10.47162/RJME.61.4.03 -
Scientific Reports Sep 2021Amantadine hydrochloride (HCl) is commonly prescribed for treating influenza A virus infection and Parkinson's disease. Recently, several studies have indicated that the...
Amantadine hydrochloride (HCl) is commonly prescribed for treating influenza A virus infection and Parkinson's disease. Recently, several studies have indicated that the use of amantadine HCl is associated with corneal edema; however, the cytotoxic effect of amantadine HCl has not been investigated. In the present study, the effects of amantadine HCl on cell growth, proliferation, and apoptosis in bovine cornea endothelial cells, and in vitro endothelial permeability were examined. Results showed that lower doses of amantadine HCl do not affect cell growth (≤ 20 μΜ), whereas higher doses of amantadine HCl inhibits cell growth (≥ 50 μΜ), induces apoptosis (2000 μΜ), increases sub-G1 phase growth arrest (2000 μΜ), causes DNA damage (≥ 1000 μΜ), and induces endothelial hyperpermeability (≥ 1000 μΜ) in bovine cornea endothelial cells; additionally, we also found that amantadine HCl attenuates the proliferation (≥ 200 μΜ) and arrests cell cycle at G1 phase (≥ 200 μΜ) in bovine cornea endothelial cells. In the present study, we measured the cytotoxic doses of amantadine HCl on cornea endothelial cells, which might be applied in evaluating the association of corneal edema.
Topics: Amantadine; Animals; Antiviral Agents; Apoptosis; Cattle; Cell Cycle; Cell Proliferation; Cells, Cultured; Cornea; Endothelial Cells; Endothelium, Corneal
PubMed: 34531501
DOI: 10.1038/s41598-021-98005-9 -
Archives of Medical Research Oct 2020SARS-Cov-2, whose symptoms include difficulty swallowing, coughing, diarrhea, and breathing failure, has caused the loss of many lives around the world. In the absence...
SARS-Cov-2, whose symptoms include difficulty swallowing, coughing, diarrhea, and breathing failure, has caused the loss of many lives around the world. In the absence of a vaccine or medication to help prevent or decrease the effects of the disease, we suggest that amantadine may reduce the effects of COVID-19.
Topics: Amantadine; Antiviral Agents; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 32571606
DOI: 10.1016/j.arcmed.2020.06.009 -
Yakugaku Zasshi : Journal of the... 2019Although the anti-influenza virus drug oseltamivir ameliorates the fever of influenza, adverse events related to its hypothermic effect have been reported. We found that... (Review)
Review
Although the anti-influenza virus drug oseltamivir ameliorates the fever of influenza, adverse events related to its hypothermic effect have been reported. We found that oseltamivir causes dose-dependent hypothermia in normal mice, and have been studying the pharmacological mechanisms responsible for 12 years. Oseltamivir blocks nicotinic cholinergic transmission at sympathetic ganglia and reduces sympathetic modulation of brown adipose tissue (BAT), a heat generator. Oseltamivir was found to target the ion channels of nicotinic acetylcholine receptors, as demonstrated by patch clamp experiments with cells expressing the human α3β4 nicotinic receptor. Metabolized oseltamivir carboxylate, which inhibits the influenza virus neuraminidase, did not elicit hypothermia and ion channel suppression. Body temperature was decreased by intracerebroventricular administration of oseltamivir. Because this hypothermic effect was inhibited by dopamine D receptor blockade, it was suggested that oseltamivir centrally stimulates the D receptor. In Japan, the package inserts for oseltamivir and amantadine indicate very similar adverse neuropsychiatric reactions for the two drugs (abnormal behavior, consciousness disturbance, convulsion, delirium, delusion, hallucination). A literature search revealed that in some previous studies, oseltamivir and amantadine were shown to block the ion channel systems and activate the dopaminergic nervous system via several mechanisms. Therefore the similarity of the adverse reactions elicited by oseltamivir and amantadine was considered attributable to their similar pharmacological effects.
Topics: Adipose Tissue, Brown; Amantadine; Animals; Antipyretics; Antiviral Agents; Body Temperature; Dose-Response Relationship, Drug; Humans; Hypothermia; Mice; Oseltamivir; Rats; Receptors, Dopamine D2; Receptors, Nicotinic
PubMed: 31061347
DOI: 10.1248/yakushi.18-00191 -
The Cochrane Database of Systematic... Sep 2020Antisocial personality disorder (AsPD) is associated with rule-breaking, criminality, substance use, unemployment, relationship difficulties, and premature death.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antisocial personality disorder (AsPD) is associated with rule-breaking, criminality, substance use, unemployment, relationship difficulties, and premature death. Certain types of medication (drugs) may help people with AsPD. This review updates a previous Cochrane review, published in 2010.
OBJECTIVES
To assess the benefits and adverse effects of pharmacological interventions for adults with AsPD.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, 13 other databases and two trials registers up to 5 September 2019. We also checked reference lists and contacted study authors to identify studies.
SELECTION CRITERIA
Randomised controlled trials in which adults (age 18 years and over) with a diagnosis of AsPD or dissocial personality disorder were allocated to a pharmacological intervention or placebo control condition.
DATA COLLECTION AND ANALYSIS
Four authors independently selected studies and extracted data. We assessed risk of bias and created 'Summary of findings tables' and assessed the certainty of the evidence using the GRADE framework. The primary outcomes were: aggression; reconviction; global state/global functioning; social functioning; and adverse events.
MAIN RESULTS
We included 11 studies (three new to this update), involving 416 participants with AsPD. Most studies (10/11) were conducted in North America. Seven studies were conducted exclusively in an outpatient setting, one in an inpatient setting, and one in prison; two studies used multiple settings. The average age of participants ranged from 28.6 years to 45.1 years (overall mean age 39.6 years). Participants were predominantly (90%) male. Study duration ranged from 6 to 24 weeks, with no follow-up period. Data were available from only four studies involving 274 participants with AsPD. All the available data came from unreplicated, single reports, and did not allow independent statistical analysis to be conducted. Many review findings were limited to descriptive summaries based on analyses carried out and reported by the trial investigators. No study set out to recruit participants on the basis of having AsPD; many participants presented primarily with substance abuse problems. The studies reported on four primary outcomes and six secondary outcomes. Primary outcomes were aggression (six studies) global/state functioning (three studies), social functioning (one study), and adverse events (seven studies). Secondary outcomes were leaving the study early (eight studies), substance misuse (five studies), employment status (one study), impulsivity (one study), anger (three studies), and mental state (three studies). No study reported data on the primary outcome of reconviction or the secondary outcomes of quality of life, engagement with services, satisfaction with treatment, housing/accommodation status, economic outcomes or prison/service outcomes. Eleven different drugs were compared with placebo, but data for AsPD participants were only available for five comparisons. Three classes of drug were represented: antiepileptic; antidepressant; and dopamine agonist (anti-Parkinsonian) drugs. We considered selection bias to be unclear in 8/11 studies, attrition bias to be high in 7/11 studies, and performance bias to be low in 7/11 studies. Using GRADE, we rated the certainty of evidence for each outcome in this review as very low, meaning that we have very little confidence in the effect estimates reported. Phenytoin (antiepileptic) versus placebo One study (60 participants) reported very low-certainty evidence that phenytoin (300 mg/day), compared to placebo, may reduce the mean frequency of aggressive acts per week (phenytoin mean = 0.33, no standard deviation (SD) reported; placebo mean = 0.51, no SD reported) in male prisoners with aggression (skewed data) at endpoint (six weeks). The same study (60 participants) reported no evidence of difference between phenytoin and placebo in the number of participants reporting the adverse event of nausea during week one (odds ratio (OR) 1.00, 95% confidence interval (CI) 0.06 to 16.76; very low-certainty evidence). The study authors also reported that no important side effects were detectable via blood cell counts or liver enzyme tests (very low-certainty evidence). The study did not measure reconviction, global/state functioning or social functioning. Desipramine (antidepressant) versus placebo One study (29 participants) reported no evidence of a difference between desipramine (250 to 300 mg/day) and placebo on mean social functioning scores (desipramine = 0.19; placebo = 0.21), assessed with the family-social domain of the Addiction Severity Index (scores range from zero to one, with higher values indicating worse social functioning), at endpoint (12 weeks) (very low-certainty evidence). Neither of the studies included in this comparison measured the other primary outcomes: aggression; reconviction; global/state functioning; or adverse events. Nortriptyline (antidepressant) versus placebo One study (20 participants) reported no evidence of a difference between nortriptyline (25 to 75 mg/day) and placebo on mean global state/functioning scores (nortriptyline = 0.3; placebo = 0.7), assessed with the Symptom Check List-90 (SCL-90) Global Severity Index (GSI; mean of subscale scores, ranging from zero to four, with higher scores indicating greater severity of symptoms), at endpoint (six months) in men with alcohol dependency (very low-certainty evidence). The study measured side effects but did not report data on adverse events for the AsPD subgroup. The study did not measure aggression, reconviction or social functioning. Bromocriptine (dopamine agonist) versus placebo One study (18 participants) reported no evidence of difference between bromocriptine (15 mg/day) and placebo on mean global state/functioning scores (bromocriptine = 0.4; placebo = 0.7), measured with the GSI of the SCL-90 at endpoint (six months) (very low-certainty evidence). The study did not provide data on adverse effects, but reported that 12 patients randomised to the bromocriptine group experienced severe side effects, five of whom dropped out of the study in the first two days due to nausea and severe flu-like symptoms (very low-certainty evidence). The study did not measure aggression, reconviction and social functioning. Amantadine (dopamine agonist) versus placebo The study in this comparison did not measure any of the primary outcomes.
AUTHORS' CONCLUSIONS
The evidence summarised in this review is insufficient to draw any conclusion about the use of pharmacological interventions in the treatment of antisocial personality disorder. The evidence comes from single, unreplicated studies of mostly older medications. The studies also have methodological issues that severely limit the confidence we can draw from their results. Future studies should recruit participants on the basis of having AsPD, and use relevant outcome measures, including reconviction.
Topics: Adult; Aggression; Alcohol-Related Disorders; Amantadine; Antisocial Personality Disorder; Anxiety; Bromocriptine; Desipramine; Female; Humans; Male; Middle Aged; Nortriptyline; Phenytoin; Placebos; Psychotropic Drugs; Randomized Controlled Trials as Topic
PubMed: 32880105
DOI: 10.1002/14651858.CD007667.pub3 -
Frontiers in Immunology 2022The influenza virus has a large clinical burden and is associated with significant mortality and morbidity. The development of effective drugs for the treatment or...
The influenza virus has a large clinical burden and is associated with significant mortality and morbidity. The development of effective drugs for the treatment or prevention of influenza is important in order to reduce its impact. Adamantanes and neuraminidase inhibitors are two classes of anti-influenza drugs in which resistance has developed; thus, there is an urgent need to explore new therapeutic options. Boosting antiviral innate immune mechanisms in the airways represents an attractive approach. Hypothiocyanite (OSCN) is produced by the airway epithelium and is effective in reducing the replication of several influenza A virus strains . It remains, however, largely unexplored whether OSCN has such an antiviral effect . Here we determined the therapeutic potential of OSCN, alone or in combination with amantadine (AMT), in preventing lethal influenza A virus replication in mice and . Mice intranasally infected with a lethal dose of A/Puerto Rico/8/1934 (H1N1) or A/Hong Kong/8/1968 (H3N2) were cured by the combination treatment of OSCN and AMT. Monotherapy with OSCN or AMT alone did not substantially improve survival outcomes. However, AMT+OSCN treatment significantly inhibited viral replication, and treatment inhibited viral entry and nuclear transport of different influenza A virus strains (H1N1 and H3N2) including the AMT-resistant strain A/WSN/33 (H1N1). A triple combination treatment consisting of AMT, oseltamivir, and OSCN was also tested and further inhibited viral replication of the AMT-resistant A/WSN/33 strain. These results suggest that OSCN is a promising anti-influenza treatment option when combined with other antiviral drugs.
Topics: Amantadine; Animals; Antiviral Agents; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza A virus; Influenza, Human; Mice; Thiocyanates
PubMed: 35663985
DOI: 10.3389/fimmu.2022.859033 -
Virus Research Aug 2014Rearrangement of the influenza A genome such that NS2 is expressed downstream of PB1 permits the insertion of a foreign gene in the NS gene segment. In this report, the...
Rearrangement of the influenza A genome such that NS2 is expressed downstream of PB1 permits the insertion of a foreign gene in the NS gene segment. In this report, the genome rearranged strategy was extended to A/California/04/2009 (pH1N1), and Gaussia luciferase (GLuc) or GFP was expressed downstream of the full-length NS1 gene (designated GLucCa04 and GFPCa04, respectively). In growth kinetics studies, culture of amantadine sensitive GLucCa04 (Sens/GlucCa04) in the presence of amantadine significantly decreased GLuc expression and viral titers for 48 h post-infection (hpi). When Sens/GlucCa04 was subsequently used in an in vitro anti-viral screening assay, amantadine treatment significantly decreased GLuc expression from amantadine sensitive compared to amantadine resistant GLucCa04 (Res/GlucCa04) as early as 16 hpi. In in vivo screening studies, DBA mice were treated daily with amantadine from 1 day prior to infection and inoculated with either Sens/GlucCa04 or Res/GlucCa04 alone or as a co-infection with the parental strain. On days 3 and 5 post-infection, lung samples were collected and amantadine treatment was shown to decrease GLuc expression by two orders of magnitude (p<0.05) in Sens/GlucCa04 infected mice. Furthermore, while both Sens and Res/GlucCa04 were highly attenuated, addition of the parental strain to the inoculum yielded clinical disease indicative of GLuc expression and pulmonary viral titers. These findings indicate that the use of GLucCa04 can potentially accelerate in vitro and in vivo anti-viral screening by shortening the time required for virus detection.
Topics: Amantadine; Animals; Antiviral Agents; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Gene Expression; Genes, Reporter; Influenza A Virus, H1N1 Subtype; Luciferases; Mice, Inbred DBA; Orthomyxoviridae Infections
PubMed: 24833536
DOI: 10.1016/j.virusres.2014.05.003 -
Alzheimer's Research & Therapy Dec 2018Cholinesterase inhibitors and memantine have been approved for management of Alzheimer's disease (AD), but there has been no consensus about the choice of various types... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cholinesterase inhibitors and memantine have been approved for management of Alzheimer's disease (AD), but there has been no consensus about the choice of various types and doses of drugs at different stages. Hence, we compared and ranked the efficacy and tolerability of these available drugs.
METHODS
We searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) published from database inception to July 21, 2017. The primary outcomes were the mean overall changes in cognitive function and responders who had any adverse events. We conducted a random-effects network meta-analysis.
RESULTS
Forty-one RCTs were included in this study. Compared with placebo, galantamine 32 mg daily (standardized mean difference - 0.51, 95% credible interval - 0.67 to - 0.35), galantamine 24 mg daily (- 0.50, - 0.61 to - 0.40), and donepezil 10 mg daily (- 0.40, - 0.51 to - 0.29) were probably the most effective agents on cognition for mild to moderate AD, and memantine 20 mg combined with donepezil 10 mg (0.76, 0.39 to 1.11) was recommended for moderate to severe patients. Memantine showed the best profile of acceptability. Rivastigmine transdermal 15-cm patch was the best optional treatment both in function and global changes. None of the medicines was likely to improve neuropsychiatric symptoms through this analysis.
CONCLUSIONS
Pharmacological interventions have beneficial effects on cognition, function, and global changes, but not on neuropsychiatric symptoms, through current network meta-analysis. The choice of drugs may mainly depend on the disease severity and clinical symptoms.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Female; Humans; Male; Memantine; Network Meta-Analysis; Nootropic Agents; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30591071
DOI: 10.1186/s13195-018-0457-9 -
Brain Research Jul 2019Environmental enrichment (EE) and amantadine (AMT) enhance motor and cognitive outcome after experimental traumatic brain injury (TBI). However, there are no data on the...
Environmental enrichment (EE) and amantadine (AMT) enhance motor and cognitive outcome after experimental traumatic brain injury (TBI). However, there are no data on the effects of combining these two therapies. Hence, the aim of the current study was to combine EE and AMT after TBI to determine if their net effect further enhances motor and cognitive performance. Anesthetized adult male rats received either a cortical impact of moderate severity or sham injury and then were randomly assigned to EE or standard (STD) housing and once daily administration of AMT (20 mg/kg; i.p.) or saline vehicle (VEH, 1 mL/kg; i.p.) beginning 24 h after injury for 19 days. Motor and cognitive function were assessed on post-surgical days 1-5 and 14-19, respectively. Cortical lesion volume was quantified on day 21. There were no statistical differences among the sham groups regardless of therapy, so the data were pooled. EE, AMT, and their combination (EE + AMT) improved beam-balance, but only EE and EE + AMT enhanced beam-walking. All three treatment paradigms improved spatial learning and memory relative to the VEH-treated STD controls (p < 0.05). No differences were revealed between the EE groups, regardless of treatment, but both were better than the AMT-treated STD group on beam-walking and spatial learning (p < 0.05). Both EE groups equally reduced cortical lesion volume relative to the STD-housed AMT and VEH groups (p < 0.05). The results indicate that although beneficial on their own, EE + AMT do not provide additional benefits after TBI. It is important to note that the lack of additive effects using the current treatment and behavioral protocols does not detract from the benefits of each individual therapy. The findings provide insight for future combination studies.
Topics: Amantadine; Animals; Brain Injuries, Traumatic; Cognition; Disease Models, Animal; Environment; Male; Maze Learning; Memory; Motor Activity; Psychomotor Performance; Rats; Rats, Sprague-Dawley; Spatial Learning
PubMed: 30876859
DOI: 10.1016/j.brainres.2019.03.007 -
Cold Spring Harbor Perspectives in... Nov 2020Influenza A virus AM2 protein is an integral membrane protein that is an ion channel (also known as a viroporin). The channel has 24 extracellular residues, 19 residues... (Review)
Review
Influenza A virus AM2 protein is an integral membrane protein that is an ion channel (also known as a viroporin). The channel has 24 extracellular residues, 19 residues that span the membrane once and acts as both the channel pore and also the membrane anchoring domain, and a 54-residue cytoplasmic tail. The M2 protein has four identical chains linked via two disulfide bonds that form a four-helix bundle that is 10-10 more permeable to protons than Na ions. The M2 channel is activated by low pH, His residue 37 is the pH sensor, and Trp residue 41 is the channel gate. The channel is blocked by the antiviral drug amantadine hydrochloride. The influenza B virus BM2 protein does not have homology with the AM2 channel, but BM2 does have the His proton sensor, Trp gate, and is activated by low pH. It is thought that the AM2 and BM2 proteins have common functions in the influenza A and B virus life cycles. Both BM2 and AM2 also facilitate virus budding. The amphipathic helix in the AM2 cytoplasmic tail has an important role in the assembly of the virus, and functional AM2 protein makes the virus independent of the "endosomal sorting complex required for transport" (ESCRT) complex scission.
Topics: Amantadine; Antiviral Agents; Humans; Influenza A virus; Influenza B virus; Ion Channels
PubMed: 31988204
DOI: 10.1101/cshperspect.a038505