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Scientific Reports Jan 2024Many COVID-19 survivors experience lingering post-COVID-19 symptoms, notably chronic fatigue persisting for months after the acute phase. Despite its prevalence, limited... (Randomized Controlled Trial)
Randomized Controlled Trial
Many COVID-19 survivors experience lingering post-COVID-19 symptoms, notably chronic fatigue persisting for months after the acute phase. Despite its prevalence, limited research has explored effective treatments for post-COVID-19 fatigue. This randomized controlled clinical trial assessed the impact of Amantadine on patients with post-COVID-19 fatigue. The intervention group received Amantadine for two weeks, while the control group received no treatment. Fatigue levels were assessed using the Visual Analog Fatigue Scale (VAFS) and Fatigue Severity Scale (FSS) questionnaires before and after the trial. At the study's onset, VAFS mean scores were 7.90 ± 0.60 in the intervention group and 7.34 ± 0.58 in the control group (P-value = 0.087). After two weeks, intervention group scores dropped to 3.37 ± 0.44, significantly lower than the control group's 5.97 ± 0.29 (P-value < 0.001). Similarly, FSS mean scores at the trial's commencement were 53.10 ± 5.96 in the intervention group and 50.38 ± 4.88 in the control group (P-value = 0.053). At the trial's end, intervention group scores decreased to 28.40 ± 2.42, markedly lower than the control group's 42.59 ± 1.50 (P-value < 0.001). In this study, we report the safety, tolerability, and substantial fatigue-relieving effects of Amantadine in post-COVID-19 fatigue. The intervention demonstrates a statistically significant reduction in fatigue levels, suggesting Amantadine's potential as an effective treatment for this persistent condition.
Topics: Humans; Multiple Sclerosis; COVID-19; Amantadine; Treatment Outcome; Surveys and Questionnaires
PubMed: 38228731
DOI: 10.1038/s41598-024-51904-z -
Turkish Journal of Medical Sciences Aug 2023Alzheimer's disease (AD) is a progressive neurodegenerative disease. Thymoquinone (TQ) has broad biological functions, including antiinflammatory, antioxidant,...
BACKGROUND
Alzheimer's disease (AD) is a progressive neurodegenerative disease. Thymoquinone (TQ) has broad biological functions, including antiinflammatory, antioxidant, neuroprotective properties. Memantine (MEM) is indicated for the symptomatic treatment of moderate to severe AD. We aimed to evaluate the effect of TQ alone or in combination with MEM on memory and hippocampal morphology in an STZ-induced rat AD model.
METHODS
Thirty male rats were included in this study. The AD model was created by giving ICV STZ. The rats were divided into 5 groups (n = 6 each). Group 1 (control group): The rats received only ICV-STZ 3 mg/kg for 2 weeks. Group 2 (sham group): In addition to ICV STZ, 9% NaCl, 1 mL/day i.p. for 2 weeks of injection, was applied. Group 3 (TQ group): In addition to ICV STZ, rats received TQ 10 mg/kg i.p. for 2 weeks. Group 4 (MEM group): In addition to ICV STZ, rats were given MEM at a dose of 5 mg/kg for two weeks. Group 5 (TQ+MEM group): In addition to ICV STZ, this group was given TQ (10 mg/kg/day, i.p.) and MEM (5 mg/kg/day, i.p.) for 2 weeks. On the 15th day, passive avoidance learning (PAL) was applied to all groups. Then, rats were sacrificed, neurons in the hippocampal CA1, CA2, CA3 regions were evaluated.
RESULTS
Groups 3, 4, 5 had longer latency periods than groups 1 and 2. The neuron density in the CA1, CA2, CA3 regions had decreased in groups 1 and 2 compared to groups 3, 4, 5. There were significantly more neurons in groups 3, 4, 5 than in groups 1 and 2.
DISCUSSION
We found that TQ alone and in combination with MEM showed ameliorative effects on memory and hippocampal morphology. TQ may offer a promising treatment strategy for AD.
Topics: Rats; Male; Animals; Alzheimer Disease; Memantine; Streptozocin; Neurodegenerative Diseases; Hippocampus; Disease Models, Animal; Maze Learning
PubMed: 38031940
DOI: 10.55730/1300-0144.5653 -
CNS Neuroscience & Therapeutics Jul 2023Increased glutamate levels and electrolytic fluctuations have been observed in acutely manic patients. Despite some efficacy of the non-competitive NMDA receptor...
INTRODUCTION
Increased glutamate levels and electrolytic fluctuations have been observed in acutely manic patients. Despite some efficacy of the non-competitive NMDA receptor antagonist memantine (Mem), such as antidepressant-like and mood-stabilizer drugs in clinical studies, its specific mechanisms of action are still uncertain. The present study aims to better characterize the Drosophila melanogaster fly Shaker mutants (SH), as a translational model of manic episodes within bipolar disorder in humans, and to investigate the potential anti-manic properties of Mem.
METHODS AND RESULTS
Our findings showed typical behavioral abnormalities in SH, which mirrored with the overexpression of NMDAR-NR1 protein subunit, matched well to glutamate up-regulation. Such molecular features were associated to a significant reduction of SH brain volume in comparison to Wild Type strain flies (WT). Here we report on the ability of Mem treatment to ameliorate behavioral aberrations of SH (similar to that of Lithium), and its ability to reduce NMDAR-NR1 over-expression.
CONCLUSIONS
Our results show the involvement of the glutamatergic system in the SH, given the interaction between the Shaker channel and the NMDA receptor, suggesting this model as a promising tool for studying the neurobiology of bipolar disorders. Moreover, our results show Mem as a potential disease-modifying therapy, providing insight on new mechanisms of action.
Topics: Animals; Humans; Memantine; Mania; Receptors, N-Methyl-D-Aspartate; Drosophila; Drosophila melanogaster; Glutamic Acid; Phenotype
PubMed: 36942502
DOI: 10.1111/cns.14145 -
RSC Advances Aug 2023A series of ten novel compounds were synthesized by incorporating a 1,3 thiazole core into amantadine and their structures were validated using different analytical and...
A series of ten novel compounds were synthesized by incorporating a 1,3 thiazole core into amantadine and their structures were validated using different analytical and spectral methods such as FTIR, EI-MS, H NMR, and C NMR. The antibacterial and enzyme inhibitory properties of these newly synthesized compounds were evaluated. Remarkably, the compounds exhibited significant antibacterial activity against and . Additionally, the inhibitory activities of the synthesized compounds, against α-amylase, α-glucosidase, and urease were investigated. Among the tested compounds, compound 6d demonstrated potent and selective inhibition of α-amylase IC = 97.37 ± 1.52 μM, while acarbose was used as positive control and exhibited IC = 5.17 ± 0.25 μM. Compound 6d and 6e exhibited prominent inhibition against α-glucosidase IC = 38.73 ± 0.80 μM and 41.63 ± 0.26 μM respectively. Furthermore, compound 6d inhibited urease with exceptional efficacy IC = 32.76 μM, while positive control thiourea showed more prominent activity having IC = 1.334 μM. Molecular docking studies disclosed the binding mechanism and affinity of these new inhibitors within the binding sites of various amino acids. To investigate the association between molecular structural characteristics and inhibitory actions of synthesized derivatives, preliminary structure-activity relationship (SAR) studies were performed. These findings indicated that compounds 6a, 6c, 6d and 6e are potential candidates for hit-to-lead follow-up in the drug-discovery process for treating diabetes and hyperglycemia.
PubMed: 37614781
DOI: 10.1039/d3ra05330j -
Archives of Rehabilitation Research and... Sep 2023Symptoms after mild traumatic brain injury (MTBI) can persist for greater than 1 month in up to 20% of individuals, yet there are no current medications approved by the...
Symptoms after mild traumatic brain injury (MTBI) can persist for greater than 1 month in up to 20% of individuals, yet there are no current medications approved by the Food and Drug Administration for treatment of specific concussion related sequelae. Amantadine, a dopamine agonist and N-Methyl-D-aspartate antagonist, is increasingly being used as a treatment option for individuals with traumatic brain injury across the spectrum of injury severity. This case report describes a 22-year-old individual who sustained an MTBI without loss of consciousness or post-traumatic amnesia after striking their head against a metal cabinet. The individual was referred to an interdisciplinary outpatient brain rehabilitation program secondary to persistent symptoms after MTBI, was prescribed amantadine for post-traumatic headache 97 days after injury, and subsequently developed symptoms of serotonin syndrome (SS) within 10 days of medication initiation. While SS caused by amantadine has been described in individuals with renal failure, this case report is the first to describe amantadine precipitating SS - confirmed by a validated diagnostic criterion and successfully treated with lorazepam and cyproheptadine - in a patient with normal renal function already on duloxetine, bupropion, and gabapentin. This case report is important in elucidating potential contributions of amantadine to the development of SS and highlighting the important role clinicians have in assessing for polypharmacy when prescribing amantadine for individuals with traumatic and acquired brain injuries.
PubMed: 37744194
DOI: 10.1016/j.arrct.2023.100283 -
Molecules (Basel, Switzerland) Nov 2023Currently, there are no effective drugs for the treatment of amyotrophic lateral sclerosis (ALS). Only two drugs-edaravone and riluzole-have been approved, but they have...
Currently, there are no effective drugs for the treatment of amyotrophic lateral sclerosis (ALS). Only two drugs-edaravone and riluzole-have been approved, but they have very limited efficacy. The aim of this work was to modify the structural core of the Edaravone-phenylpyrazolone moiety and combine it with aminoadamantane pharmacophore in order to expand the spectrum of its action to a number of processes involved in the pathogenesis of ALS. New conjugates of edaravone derivatives with 1-aminoadamantanes combined with alkylene or hydroxypropylene spacers were synthesized, and their biological activity was investigated. Compounds were found that could inhibit lipid peroxidation and calcium-related mitochondrial permeability, block fast sodium currents of CNS neurons, and reduce aggregation of the mutated form of the FUS-protein typical to ALS. So, the proposed modification of the edaravone molecule has allowed the obtaining of new original structures that combine some prospective therapeutic mechanisms against key chains of the pathogenesis of ALS. The identified lead compounds can be used for further optimization and development of new promising drugs on this basis for the treatment of ALS.
Topics: Humans; Edaravone; Neuroprotective Agents; Amyotrophic Lateral Sclerosis; Adamantane; Riluzole; Amantadine
PubMed: 38005288
DOI: 10.3390/molecules28227567 -
Water Research Jun 2023Wastewater-based epidemiology (WBE) is a promising technique for monitoring the rapidly increasing use of antiviral drugs during the COVID-19 pandemic. It is essential...
Wastewater-based epidemiology (WBE) is a promising technique for monitoring the rapidly increasing use of antiviral drugs during the COVID-19 pandemic. It is essential to evaluate the in-sewer stability of antiviral drugs in order to determine appropriate biomarkers. This study developed an analytical method for quantification of 17 typical antiviral drugs, and investigated the stability of target compounds in sewer through 4 laboratory-scale gravity sewer reactors. Nine antiviral drugs (lamivudine, acyclovir, amantadine, favipiravir, nevirapine, oseltamivir, ganciclovir, emtricitabine and telbivudine) were observed to be stable and recommended as appropriate biomarkers for WBE. As for the other 8 unstable drugs (abacavir, arbidol, ribavirin, zidovudine, ritonavir, lopinavir, remdesivir and efavirenz), their attenuation was driven by adsorption, biodegradation and diffusion. Moreover, reaction kinetics revealed that the effects of sediments and biofilms were regarded to be independent in gravity sewers, and the rate constants of removal by biofilms was directly proportional to the ratio of surface area against wastewater volume. The study highlighted the potential importance of flow velocity for compound stability, since an increased flow velocity significantly accelerated the removal of unstable biomarkers. In addition, a framework for graded evaluation of biomarker stability was proposed to provide reference for researchers to select suitable WBE biomarkers. Compared with current classification method, this framework considered the influences of residence time and different removal mechanisms, which additionally screened four antiviral drugs as viable WBE biomarkers. This is the first study to report the stability of antiviral drugs in gravity sewers.
Topics: Humans; Sewage; Wastewater-Based Epidemiological Monitoring; Antiviral Agents; Pandemics; Water Pollutants, Chemical; COVID-19; Biomarkers
PubMed: 37150064
DOI: 10.1016/j.watres.2023.120023 -
Biomedicine & Pharmacotherapy =... Aug 2023Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist used in the treatment of Alzheimer's disease (AD). NMDA receptors are expressed on bone cells. The aim of...
Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist used in the treatment of Alzheimer's disease (AD). NMDA receptors are expressed on bone cells. The aim of the present study was to investigate the effects of memantine on the rat musculoskeletal system. Taking into account that most of female AD patients are postmenopausal, the study was carried out on intact and ovariectomized (estrogen-deficient) rats. Mature Wistar rats were divided into following groups: non-ovariectomized (NOVX) control rats, NOVX rats treated with memantine, ovariectomized (OVX) control rats, and OVX rats treated with memantine. Memantine (2 mg/kg p.o.) was administered once daily for four weeks, starting one week after ovariectomy. The serum bone turnover marker and cytokine levels, bone density, mass, mineralization, mechanical properties, histomorphometric parameters of compact and cancellous bone, skeletal muscle mass and grip strength were determined. In NOVX rats, memantine slightly decreased the strength of compact bone of the femoral diaphysis (parameters in the yield point) and unfavorably affected histomorphometric parameters of cancellous bone (the femoral epiphysis and metaphysis). In OVX rats, in which estrogen deficiency induced osteoporotic changes, memantine increased the phosphorus content in the femoral bone mineral. No other effects on bone were observed in the memantine-treated OVX rats. In conclusion, the results of the present study indicated slight damaging skeletal effects of memantine in rats with normal estrogen levels.
Topics: Rats; Female; Animals; Humans; Rats, Wistar; Memantine; Bone and Bones; Estrogens; Bone Density; Ovariectomy
PubMed: 37229803
DOI: 10.1016/j.biopha.2023.114921 -
Neuropediatrics Apr 2024The risk factors for respiratory insufficiency in children with Guillain-Barré syndrome (GBS) are poorly known. This study aimed to investigate the factors associated...
OBJECTIVE
The risk factors for respiratory insufficiency in children with Guillain-Barré syndrome (GBS) are poorly known. This study aimed to investigate the factors associated with respiratory insufficiency in children with GBS.
METHODS
This retrospective study included children diagnosed with GBS by pediatric neurologists and admitted at the Wuhan Children's Hospital and other hospitals from January 2013 to October 2022. The patients were divided into the respiratory insufficiency and nonrespiratory insufficiency groups according to whether they received assist breathing during treatment.
RESULTS
The median (interquartile range) age of onset of 103 patients were 5 (3.1-8.5) years, 69 (67%) were male, and 64 (62.1%) had a history of precursor infection. Compared with the nonrespiratory insufficiency group, the respiratory insufficiency group showed more facial and/or bulbar weakness ( = 0.002), a higher Hughes Functional Grading Scale (HFGS) at admission ( < 0.001), and a shorter onset-to-admission interval ( = 0.017). Compared with the acute motor axonal neuropathy (AMAN) subtype, the acute inflammatory demyelinating polyneuropathy (AIDP) subtype showed longer days from onset to lumbar ( = 0.000), lower HFGS at admission ( = 0.04), longer onset-to-admission interval ( = 0.001), and more cranial nerve involvement ( = 0.04). The incidence of respiratory insufficiency between AIDP and AMAN showed no statistical difference ( > 0.05).
CONCLUSION
In conclusion, facial and/or bulbar weakness, HFGS at admission, and onset-to-admission interval were associated with respiratory insufficiency and might be useful prognostic markers in children with GBS.
Topics: Child; Humans; Male; Child, Preschool; Female; Guillain-Barre Syndrome; Retrospective Studies; Hospitalization; Respiratory Insufficiency; Amantadine
PubMed: 38253279
DOI: 10.1055/s-0043-1777767 -
Virology Journal Jul 2023SARS-CoV-2 has caused a worldwide pandemic since December 2019 and the search for pharmaceutical targets against COVID-19 remains an important challenge. Here, we...
BACKGROUND
SARS-CoV-2 has caused a worldwide pandemic since December 2019 and the search for pharmaceutical targets against COVID-19 remains an important challenge. Here, we studied the envelope protein E of SARS-CoV and SARS-CoV-2, a highly conserved 75-76 amino acid viroporin that is crucial for virus assembly and release. E protein channels were recombinantly expressed in HEK293 cells, a membrane-directing signal peptide ensured transfer to the plasma membrane.
METHODS
Viroporin channel activity of both E proteins was investigated using patch-clamp electrophysiology in combination with a cell viability assay. We verified inhibition by classical viroporin inhibitors amantadine, rimantadine and 5-(N,N-hexamethylene)-amiloride, and tested four ivermectin derivatives.
RESULTS
Classical inhibitors showed potent activity in patch-clamp recordings and viability assays. In contrast, ivermectin and milbemycin inhibited the E channel in patch-clamp recordings but displayed only moderate activity on the E protein in the cell viability assay, which is also sensitive to general cytotoxic activity of the tested compounds. Nemadectin and ivermectin aglycon were inactive. All ivermectin derivatives were cytotoxic at concentrations > 5 µM, i.e. below the level required for E protein inhibition.
CONCLUSIONS
This study demonstrates direct inhibition of the SARS-CoV-2 E protein by classical viroporin inhibitors. Ivermectin and milbemycin inhibit the E protein channel but their cytotoxicity argues against clinical application.
Topics: Humans; Viroporin Proteins; SARS-CoV-2; Cell Survival; HEK293 Cells; Ivermectin; COVID-19; Severe acute respiratory syndrome-related coronavirus
PubMed: 37422646
DOI: 10.1186/s12985-023-02095-y