-
International Journal of Physiology,... 2021Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus disease 2019 (COVID-19)... (Review)
Review
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus disease 2019 (COVID-19) is chronic, inflammatory. Although the exact mechanisms of COVID-19 have not been yet discovered some drugs are found helpful for its treatment. These drugs which are divided into some lines therapies, have demonstrated to be helpful for COVID-19 patients based on immune basic and its antiviral properties of the disease. Previous studies have been indicated that deterioration of COVID-19 condition is associated with a weaker immune system. Most of these therapies impact on the immune system and immune cells. Beside many beneficial effects of these drugs, some adverse effects (AE) have been reported in many experiments and clinical trials among patients suffering from COVID-19. In this review, we conclude some AEs of vitamin-D, zinc, remdesivir, hydroxychloroquine or chloroquine, azithromycin, dexamethasone, amantadine, aspirin reported in different papers and we continue the rest of the drugs in second part of our review article.
PubMed: 34540130
DOI: No ID Found -
Folia Neuropathologica 2021The majority of COVID-19 cases are only mildly or moderately symptomatic, but in some patients excessive inflammatory response becomes the dominant factor of disease... (Review)
Review
The majority of COVID-19 cases are only mildly or moderately symptomatic, but in some patients excessive inflammatory response becomes the dominant factor of disease progression to the advanced stage, with high mortality. Treatment with anti-inflammatory drugs either does not prevent disease progression (non-steroidal anti-inflammatory drugs [NSAIDs], colchicine), or is recommended only at the advanced disease stage (dexamethasone). Fluvoxamine and amantadine are drugs used to treat neurological and psychiatric diseases. Fluvoxamine is a selective serotonin uptake inhibitor, whereas amantadine is an old antiviral variably influencing brain neurotransmitter systems, and repurposed to Parkinson's disease. Both drugs are agonists of sigma-1 receptors located in the endoplasmic reticulum, which effect seems responsible for their anti-inflammatory activity. Moreover, amantadine was found to dampen the expression of cathepsin-L, a lysosomal enzyme implicated in SARS-CoV-2 virus entry to target cells. In two small controlled clinical trials, early treatment of SARS-CoV-2-infected persons with fluvoxamine fully prevented COVID-19 symptoms. Anecdotal evidence shows that amantadine may be similarly effective. Both drugs are easily available, inexpensive and have favorable safety profiles. Clinical trials evaluating their efficacy as much-needed post-exposure prophylaxis and early treatment of COVID-19 are ongoing.
Topics: Anti-Inflammatory Agents; Antiviral Agents; COVID-19; Central Nervous System Agents; Humans; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34284539
DOI: 10.5114/fn.2021.107572 -
Parkinson's Disease 2019Since the discovery of levodopa (L-dopa) in 1967, the range of medications available to treat Parkinson's disease has increased significantly and guidance on the use,... (Review)
Review
Since the discovery of levodopa (L-dopa) in 1967, the range of medications available to treat Parkinson's disease has increased significantly and guidance on the use, efficacy, and safety of these medications has evolved. To assess levels of adherence to national prescribing guidelines and awareness of changes in the efficacy and safety data published in the profiles of medications for the treatment of PD, we have reviewed studies on patterns and determinants of prescribing PD medications conducted in the last 50 years (since the discovery of L-dopa). A systematic literature review was conducted using EMBASE (1967 to March, 2018), Ovid MEDLINE(R) ALL (1967 to March 16, 2018), PsycINFO (1967 to the 2 week of March, 2018), and PubMed to identify all studies measuring prescribing patterns of PD medication between 1967 and 2017. Study design, source of data, country, year of study, number of patients and/or prescriptions, unit of analysis, prescribing determinants, and percentage utilisation of PD medications were extracted where possible. 44 studies examining prescribing patterns and/or prescribing determinants across 17 countries were identified. Unsurprisingly, L-dopa was the most commonly prescribed medication in all studies, accounting for 46.50% to 100% of all prescriptions for PD. In several studies, the prescribing rate of ergot-derived dopamine agonists (DAs) decreased over time in concordance with guidance. In contrast, the prescribing rates of non-ergot DAs increased over the last ten years in most of the included studies. In examining prescribing factors, two major categories were exemplified, patients' factors and prescribers' factors, with patients' age being the most common factor that affected the prescription in most studies. In conclusion, L-dopa is now the most commonly prescribed medication for cases of PD but there is large variation in the prescribing rates of catechol-O-methyltransferase (COMT) inhibitors, monoamine oxidase B (MAO-B) inhibitors, amantadine, and anticholinergics between countries. New studies examining the effects of recent clinical trials and measuring the prescribing rates of newly approved medications are warranted.
PubMed: 31781365
DOI: 10.1155/2019/9237181 -
Epilepsia Dec 2023N-methyl-d-aspartate (NMDA) receptors are expressed at synaptic sites, where they mediate fast excitatory neurotransmission. NMDA receptors are critical to brain...
OBJECTIVE
N-methyl-d-aspartate (NMDA) receptors are expressed at synaptic sites, where they mediate fast excitatory neurotransmission. NMDA receptors are critical to brain development and cognitive function. Natural variants to the GRIN1 gene, which encodes the obligatory GluN1 subunit of the NMDA receptor, are associated with severe neurological disorders that include epilepsy, intellectual disability, and developmental delay. Here, we investigated the pathogenicity of three missense variants to the GRIN1 gene, p. Ile148Val (GluN1-3b[I481V]), p.Ala666Ser (GluN1-3b[A666S]), and p.Tyr668His (GluN1-3b[Y668H]).
METHODS
Wild-type and variant-containing NMDA receptors were expressed in HEK293 cells and primary hippocampal neurons. Patch-clamp electrophysiology and pharmacology were used to profile the functional properties of the receptors. Receptor surface expression was evaluated using fluorescently tagged receptors and microscopy.
RESULTS
Our data demonstrate that the GluN1(I481V) variant is inhibited by the open pore blockers ketamine and memantine with reduce potency but otherwise has little effect on receptor function. By contrast, the other two variants exhibit gain-of-function molecular phenotypes. Glycine sensitivity was enhanced in receptors containing the GluN1(A666S) variant and the potency of pore block by memantine and ketamine was reduced, whereas that for MK-801 was increased. The most pronounced functional deficits, however, were found in receptors containing the GluN1(Y668H) variant. GluN1(Y668H)/2A receptors showed impaired surface expression, were more sensitive to glycine and glutamate by an order of magnitude, and exhibited impaired block by extracellular magnesium ions, memantine, ketamine, and MK-801. These variant receptors were also activated by either glutamate or glycine alone. Single-receptor recordings revealed that this receptor variant opened to several conductance levels and activated more frequently than wild-type GluN1/2A receptors.
SIGNIFICANCE
Our study reveals a critical functional locus of the receptor (GluN1[Y668]) that couples receptor gating to ion channel conductance, which when mutated may be associated with neurological disorder.
Topics: Humans; Memantine; Dizocilpine Maleate; Receptors, N-Methyl-D-Aspartate; Ketamine; HEK293 Cells; Glutamates; Neurodevelopmental Disorders; Glycine; Nerve Tissue Proteins
PubMed: 37734923
DOI: 10.1111/epi.17776 -
Neuropsychiatric Disease and Treatment 2023Fatigue is a common, debilitating and often underestimated symptom in patients with multiple sclerosis (MS). The exact pathophysiological mechanism of fatigue in MS is... (Review)
Review
Fatigue is a common, debilitating and often underestimated symptom in patients with multiple sclerosis (MS). The exact pathophysiological mechanism of fatigue in MS is still unknown. However, there are many theories involving different immunological, metabolic and inflammatory mechanisms of fatigue. Owing to the subjective nature of this symptom, its diagnosis is still very limited and is still based only on diagnostic questionnaires. Although several therapeutic agents have been used in the past to try to influence fatigue in MS patients, no single effective approach for the treatment of fatigue has yet been found. This review article aims to provide the reader with information on the current theories on the origin and mechanism of fatigue in MS, as well as diagnostic procedures and, finally, current therapeutic strategies for the management of fatigue in MS patients.
PubMed: 38029042
DOI: 10.2147/NDT.S429862 -
The Turkish Journal of Pediatrics 2023Catatonia is a complex neuropsychiatric disorder involving stupor, waxy flexibility, and mutism lasting more than 1 hour. It has arisen mostly from mental and neurologic...
BACKGROUND
Catatonia is a complex neuropsychiatric disorder involving stupor, waxy flexibility, and mutism lasting more than 1 hour. It has arisen mostly from mental and neurologic disorders. Organic causes are more prominent in children.
CASE
A 15-year-old female who had refused to eat and drink for 3 days, had not talked, and had stood in a fixed position for long periods was admitted to the inpatient clinic, and she was diagnosed with catatonia. Her maximum score on the Bush-Francis Catatonia Rating Scale (BFCRS) was 15/69 on day 2 of her stay. On neurologic examination, the patient`s cooperation was limited, and she was apathetic to her surroundings and stimuli and inactive. Other neurologic examination findings were normal. To investigate catatonia etiology, her biochemical parameters, thyroid hormone panel, and toxicology screening were conducted but all parameters were normal. Cerebrospinal fluid examination and autoimmune antibodies were negative. Sleep electroencephalography showed diffuse slow background activity, and brain magnetic resonance imaging was normal. As a first-line treatment for catatonia, diazepam was started. With her poor response to diazepam, we continued to evaluate the cause and found the transglutaminase levels were 153 U/mL (normal values, < 10 U/mL). The patient`s duodenal biopsies showed changes consistent with Celiac disease (CD). Catatonic symptoms did not benefit from a gluten-free diet or oral diazepam for 3 weeks. Then, diazepam was replaced with amantadine. With amantadine, the patient recovered within 48 hours, and her BFCRS retreated to 8/69.
CONCLUSIONS
Even without gastrointestinal manifestations, CD may present with neuropsychiatric symptoms. According to this case report, CD should be investigated in patients with unexplained catatonia, and that CD may only present with neuropsychiatric symptoms.
Topics: Child; Female; Humans; Adolescent; Catatonia; Celiac Disease; Amantadine; Biopsy; Diazepam
PubMed: 36866995
DOI: 10.24953/turkjped.2022.411 -
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 -
Microorganisms Jan 2023Influenza infection is serious and debilitating for humans and animals. The influenza virus undergoes incessant mutation, segment recombination, and genome reassortment.... (Review)
Review
Influenza infection is serious and debilitating for humans and animals. The influenza virus undergoes incessant mutation, segment recombination, and genome reassortment. As a result, new epidemics and pandemics are expected to emerge, making the elimination challenging of the disease. Antiviral therapy has been used for the treatment of influenza since the development of amantadine in the 1960s; however, its use is hampered by the emergence of novel strains and the development of drug resistance. Thus, combinational therapy with two or more antivirals or immunomodulators with different modes of action is the optimal strategy for the effective treatment of influenza infection. In this review, we describe current options for combination therapy, their performance, and constraints imposed by resistance, calling attention to the advantages of combination therapy against severe influenza infections. We also discuss the challenges of influenza therapy and the limitations of approved antiviral drugs.
PubMed: 36677475
DOI: 10.3390/microorganisms11010183 -
The Malaysian Journal of Pathology Aug 2020The commonest cause of dementia among the elderly population is Alzheimer's disease (AD). It is a health concern globally as the number of people affected by dementia... (Review)
Review
The commonest cause of dementia among the elderly population is Alzheimer's disease (AD). It is a health concern globally as the number of people affected by dementia worldwide is rapidly increasing. Several genes have been linked to AD and the pathogenesis of the disease has been extensively and vigorously examined. Thus far, only a few drugs have been approved by the Food and Drug Administration (FDA) for the pharmacological treatment of AD and a growing body of research has turned to alternative options such as stem cell therapy. This review will give an overview of the pathological and clinical aspects of AD. Although researchers have explored the suitability and feasibility of using various types of stems cells to treat AD, this review will focus mainly on neural stem cells (NSCs)/ neural progenitor cells (NPCs). The behaviour and properties of NSCs will be described, accompanied by a comprehensive discussion of the therapeutic strategies involving the use of NSCs/NPCs in the treatment of the disease.
Topics: Aged; Alzheimer Disease; Cell Differentiation; Cholinesterase Inhibitors; Humans; Memantine; Neural Stem Cells; Neurogenesis; Stem Cell Transplantation; Stem Cells
PubMed: 32860368
DOI: No ID Found -
BMC Neuroscience Dec 2022Balance and memory deficits are common in patients with repetitive mild traumatic brain injury (mTBI).
BACKGROUND
Balance and memory deficits are common in patients with repetitive mild traumatic brain injury (mTBI).
OBJECTIVE
To investigate the combined effects of amantadine and transcranial direct current stimulation (tDCS) on balance and memory in repetitive mTBI rat models.
METHODS
In this prospective animal study, 40 repetitive mTBI rats were randomly assigned to four groups: tDCS, amantadine, combination of amantadine and anodal tDCS, and control. The tDCS group received four sessions of anodal tDCS for four consecutive days. The amantadine group received four intraperitoneal injections of amantadine for four consecutive days. The combination group received four intraperitoneal injections of amantadine and anodal tDCS for four consecutive days. Motor-evoked potential (MEP), rotarod test, and novel object test results were evaluated before mTBI, before treatment, and after treatment.
RESULTS
All groups showed significant improvements in the rotarod and novel object tests, particularly the combination group. The combination group showed a significant improvements in duration (p < 0.01) and maximal speed in the rotarod test (p < 0.01), as well as an improvement in novel object ratio (p = 0.05) and MEP amplitude (p = 0.05) after treatment. The combination group exhibited a significant increase in novel object ratio compared to the tDCS group (p = 0.04). The GFAP integral intensity of the left motor cortex and hippocampus was the lowest in the combination group.
CONCLUSION
Combination treatment with amantadine and tDCS had positive effects on balance and memory recovery after repetitive mTBI in rats. Therefore, we expect that the combination of amantadine and tDCS may be a treatment option for patients with repetitive mTBIs.
Topics: Animals; Rats; Transcranial Direct Current Stimulation; Brain Concussion; Prospective Studies; Evoked Potentials, Motor; Motor Cortex
PubMed: 36503366
DOI: 10.1186/s12868-022-00763-3