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Current Neuropharmacology 2022Despite increasing worldwide incidence of Parkinson's disease, the therapy is still suboptimal due to the diversified clinical manifestations, lack of sufficient...
BACKGROUND
Despite increasing worldwide incidence of Parkinson's disease, the therapy is still suboptimal due to the diversified clinical manifestations, lack of sufficient treatment, the poor adherence in advanced patients, and varied response. Proper intake of medications regarding food and managing drug-food interactions may optimize Parkinson's disease treatment.
OBJECTIVES
We investigated potential effects that food, beverages, and dietary supplements may have on the pharmacokinetics and pharmacodynamics of drugs used by parkinsonian patients; identified the most probable interactions; and shaped recommendations for the optimal intake of drugs regarding food.
METHODS
We performed a systematic review in adherence to PRISMA guidelines, and included a total of 81 studies in the qualitative synthesis.
RESULTS AND CONCLUSION
We found evidence for levodopa positive interaction with coffee, fiber and vitamin C, as well as for the potential beneficial impact of low-fat and protein redistribution diet. Contrastingly, high-protein diet and ferrous sulfate supplements can negatively affect levodopa pharmacokinetics and effectiveness. For other drugs, the data of food impact are scarce. Based on the available limited evidence, all dopamine agonists (bromocriptine, cabergoline, ropinirole), tolcapone, rasagiline, selegiline in tablets, safinamide, amantadine and pimavanserin can be taken with or without a meal. Opicapone and orally disintegrating selegiline tablets should be administered on an empty stomach. Of monoamine oxidase B inhibitors, safinamide is the least susceptible for interaction with the tyramine-rich food, whereas selegiline and rasagiline may lose selectivity to monoamine oxidase B when administered in supratherapeutic doses. The level of presented evidence is low due to the poor studies design, their insufficient actuality, and missing data.
Topics: Antiparkinson Agents; Dietary Supplements; Humans; Levodopa; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Parkinson Disease; Selegiline
PubMed: 34784871
DOI: 10.2174/1570159X19666211116142806 -
Cureus Aug 2020The adverse events of antiviral drugs are dose-dependent and often reversible. The nervous system is often affected and to date, many studies have been... (Review)
Review
The adverse events of antiviral drugs are dose-dependent and often reversible. The nervous system is often affected and to date, many studies have been published regarding the central nervous system toxicity of antiviral agents. They may cause significant neuropsychiatric complications, which range from mild symptoms such as irritability and difficulty sleeping to severe complications such as depression, psychosis, and painful peripheral neuropathy, side effects which may necessitate discontinuation of treatment. The pathogenetic mechanisms may involve molecular targets common to other centrally active drugs, including human monoamine oxidase-A (MAO-A), serotonin receptors, gamma-aminobutyric acid (GABA) GABA-A receptors, 5-HT2A and 5-HT2C receptors and others. Notable examples include oseltamivir which may act as MAO inhibitor and efavirenz, which has an affinity for serotonin 5-HT2 and GABA-A receptors, the serotonin transporter, the MAO enzyme, and the vesicular monoamine transporter, with subjective effects which may be similar to those of the psychedelic hallucinogen lysergic acid diethylamide (LSD). Other antiviral drugs with prominent nervous system effects include nucleoside reverse transcriptase inhibitors, which are associated with the development of peripheral neuropathy after prolonged use (an effect strongly associated with older drugs which have since fallen into disfavor such as stavudine) and interferons, which may cause depression. Clinicians should be familiar with such adverse effects in order to recognise them promptly once they occur and manage them appropriately.
PubMed: 32905132
DOI: 10.7759/cureus.9536 -
Nature Metabolism Sep 2020Type 1 diabetes (T1D) is caused by the autoimmune destruction of pancreatic beta cells. Pluripotent stem cells can now be differentiated into beta cells, thus raising...
Type 1 diabetes (T1D) is caused by the autoimmune destruction of pancreatic beta cells. Pluripotent stem cells can now be differentiated into beta cells, thus raising the prospect of a cell replacement therapy for T1D. However, autoimmunity would rapidly destroy newly transplanted beta cells. Using a genome-scale CRISPR screen in a mouse model for T1D, we show that deleting RNLS, a genome-wide association study candidate gene for T1D, made beta cells resistant to autoimmune killing. Structure-based modelling identified the U.S. Food and Drug Administration-approved drug pargyline as a potential RNLS inhibitor. Oral pargyline treatment protected transplanted beta cells in diabetic mice, thus leading to disease reversal. Furthermore, pargyline prevented or delayed diabetes onset in several mouse models for T1D. Our results identify RNLS as a modifier of beta cell vulnerability and as a potential therapeutic target to avert beta cell loss in T1D.
Topics: Animals; Autoimmunity; CRISPR-Cas Systems; Diabetes Mellitus, Type 1; Endoplasmic Reticulum Stress; Enzyme Inhibitors; Female; Genome-Wide Association Study; Induced Pluripotent Stem Cells; Insulin-Secreting Cells; Islets of Langerhans Transplantation; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, Knockout; Monoamine Oxidase; Mutation; Pargyline
PubMed: 32719542
DOI: 10.1038/s42255-020-0254-1 -
Journal of Neural Transmission (Vienna,... Feb 2020Monoamine oxidase (MAO) plays a central role in the metabolism of the neurotransmitters dopamine, norepinephrine, and serotonin. This brief review focuses on... (Review)
Review
Monoamine oxidase (MAO) plays a central role in the metabolism of the neurotransmitters dopamine, norepinephrine, and serotonin. This brief review focuses on 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is the immediate product of MAO acting on cytoplasmic dopamine. DOPAL is toxic; however, normally DOPAL is converted via aldehyde dehydrogenase (ALDH) to 3,4-dihydroxyphenylacetic acid (DOPAC), which rapidly exits the neurons. In addition to vesicular uptake of dopamine via the vesicular monoamine transporter (VMAT), the two-enzyme sequence of MAO and ALDH keeps cytoplasmic dopamine levels low. Dopamine oxidizes readily to form toxic products that could threaten neuronal homeostasis. The catecholaldehyde hypothesis posits that diseases featuring catecholaminergic neurodegeneration result from harmful interactions between DOPAL and the protein alpha-synuclein, a major component of Lewy bodies in diseases such as Parkinson disease, dementia with Lewy bodies, and pure autonomic failure. DOPAL potently oligomerizes alpha-synuclein, and alpha-synuclein oligomers impede vesicular functions, shifting the fate of cytoplasmic dopamine toward MAO-catalyzed formation of DOPAL-a vicious cycle. When MAO deaminates dopamine to form DOPAL, hydrogen peroxide is generated; and DOPAL, hydrogen peroxide, and divalent metal cations react to form hydroxyl radicals, which peroxidate lipid membranes. Lipid peroxidation products in turn inhibit ALDH, causing DOPAL to accumulate-another vicious cycle. MAO inhibition decreases DOPAL formation but concurrently increases the spontaneous oxidation of dopamine, potentially trading off one form of toxicity for another. These considerations rationalize a neuroprotection strategy based on concurrent treatment with an MAO inhibitor and an anti-oxidant.
Topics: 3,4-Dihydroxyphenylacetic Acid; Aldehyde Dehydrogenase; Animals; Dopamine; Humans; Monoamine Oxidase; Neurodegenerative Diseases; Neurons
PubMed: 31807952
DOI: 10.1007/s00702-019-02106-9 -
Scientific Reports Nov 2023Monoamine oxidase B (MAO-B) inhibitors are used to control Parkinson's disease (PD). Selegiline, rasagiline, and safinamide are widely used as MAO-B inhibitors...
Monoamine oxidase B (MAO-B) inhibitors are used to control Parkinson's disease (PD). Selegiline, rasagiline, and safinamide are widely used as MAO-B inhibitors worldwide. Although these drugs inhibit MAO-B, there are pharmacological and chemical differences, such as the inhibitory activity, the non-dopaminergic properties in safinamide, and the amphetamine-like structure in selegiline. MAO-B inhibitors may differ in adverse events (AEs). However, differences in actual practical clinics are not fully investigated. A retrospective study was conducted using FAERS, the largest database of spontaneous adverse events. AE signals for MAO-B inhibitors, including selegiline, rasagiline, and safinamide, were detected using the reporting odds ratio method and compared. Hypocomplementemia, hepatic cyst, hepatic function abnormal, liver disorder and cholangitis were detected for selegiline as drug-specific signals. The amphetamine effect was not confirmed for any of the three MAO-B inhibitors. The tyramine reaction was detected as an AE signal only for rasagiline. Moreover, the REM sleep behavior disorder was not detected as an AE signal for safinamide, suggesting that non-dopaminergic effects might be beneficial. Considering the differences in AEs for MAO-B inhibitors will assist with the appropriate PD medication.
Topics: Humans; Monoamine Oxidase Inhibitors; Parkinson Disease; Selegiline; Retrospective Studies; Monoamine Oxidase; Dopamine Agents; Amphetamines
PubMed: 37935702
DOI: 10.1038/s41598-023-44142-2 -
Journal of Psychopharmacology (Oxford,... Feb 2022Recent studies have suggested that microglial activation plays a key role in the pathogenesis of depression. In fact, neuroinflammation is associated with a phenotypic... (Review)
Review
BACKGROUND
Recent studies have suggested that microglial activation plays a key role in the pathogenesis of depression. In fact, neuroinflammation is associated with a phenotypic change of microglia, consisting of morphological differences, increased release of cytokines and oxidative stress products, which may contribute to the development and maintenance of depression. Antidepressants, including selective serotonin re-uptake inhibitors and serotonin-norepinephrine reuptake inhibitors, have been shown to act on the immune and oxidative stress mechanisms commonly found to be disrupted in depression. Thus, the inhibition of microglial activation may be one of the mechanisms through which they exert an antidepressant action.
AIM
This is the first review summarising in vitro and ex vivo studies investigating the effects of different classes of antidepressants on microglia activation, by examining cellular changes and/or via measuring the production of immune and/or oxidative stress signalling molecules, in microglia models of neuroinflammation with either lipopolysaccharide (LPS) or cytokines. A total of 23 studies were identified, 18 using LPS stimulation and 5 using cytokines stimulation.
RESULTS
Overall, the studies show that antidepressants, such as selective serotonin re-uptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors and tricyclic antidepressants prevented microglial activation, including reduced microglial reactivity and decreased immune and oxidative stress products, in both models. However, specific antidepressants, such as bupropion and agomelatine did not prevent interferon-gamma (IFN-γ)-induced microglial activation; and for other antidepressants, including phenelzine, venlafaxine and sertraline, the results of different studies were inconsistent.
CONCLUSIONS
Overall, results summarised in this review support the hypothesis that the action of at least certain classes of antidepressants may involve regulation of microglial activation, especially when in presence of increased levels of inflammation.
Topics: Animals; Antidepressive Agents; Depression; Humans; Microglia; Neuroinflammatory Diseases; Oxidative Stress; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 35098788
DOI: 10.1177/02698811211069110 -
Journal of Enzyme Inhibition and... Dec 2023Alzheimer's disease (AD) is a progressive brain disease characterised by progressive memory loss and cognition impairment, ultimately leading to death. There are three... (Review)
Review
Alzheimer's disease (AD) is a progressive brain disease characterised by progressive memory loss and cognition impairment, ultimately leading to death. There are three FDA-approved acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine, AChEIs) for the symptomatic treatment of AD. Monoamine oxidase B (MAO-B) has been considered to contribute to pathologies of AD. Therefore, we reviewed the dual inhibitors of acetylcholinesterase (AChE) and MAO-B developed in the last five years. In this review, these dual-target inhibitors were classified into six groups according to the basic parent structure, including chalcone, coumarin, chromone, benzo-fused five-membered ring, imine and hydrazine, and other scaffolds. Their design strategies, structure-activity relationships (SARs), and molecular docking studies with AChE and MAO-B were analysed and discussed, giving valuable insights for the subsequent development of AChE and MAO-B dual inhibitors. Challenges in the development of balanced and potent AChE and MAO-B dual inhibitors were noted, and corresponding solutions were provided.
Topics: Humans; Monoamine Oxidase; Acetylcholinesterase; Alzheimer Disease; Monoamine Oxidase Inhibitors; Molecular Docking Simulation; Cholinesterase Inhibitors; Structure-Activity Relationship
PubMed: 37955252
DOI: 10.1080/14756366.2023.2270781 -
Molecules (Basel, Switzerland) Jun 2023With the significant growth of patients suffering from neurodegenerative diseases (NDs), novel classes of compounds targeting monoamine oxidase type B (MAO-B) are... (Review)
Review
With the significant growth of patients suffering from neurodegenerative diseases (NDs), novel classes of compounds targeting monoamine oxidase type B (MAO-B) are promptly emerging as distinguished structures for the treatment of the latter. As a promising function of computer-aided drug design (CADD), structure-based virtual screening (SBVS) is being heavily applied in processes of drug discovery and development. The utilization of molecular docking, as a helping tool for SBVS, is providing essential data about the poses and the occurring interactions between ligands and target molecules. The current work presents a brief discussion of the role of MAOs in the treatment of NDs, insight into the advantages and drawbacks of docking simulations and docking software, and a look into the active sites of MAO-A and MAO-B and their main characteristics. Thereafter, we report new chemical classes of MAO-B inhibitors and the essential fragments required for stable interactions focusing mainly on papers published in the last five years. The reviewed cases are separated into several chemically distinct groups. Moreover, a modest table for rapid revision of the revised works including the structures of the reported inhibitors together with the utilized docking software and the PDB codes of the crystal targets applied in each study is provided. Our work could be beneficial for further investigations in the search for novel, effective, and selective MAO-B inhibitors.
Topics: Humans; Monoamine Oxidase Inhibitors; Molecular Docking Simulation; Monoamine Oxidase; Drug Discovery; Drug Design; Structure-Activity Relationship
PubMed: 37375370
DOI: 10.3390/molecules28124814 -
ACS Omega Oct 2023The monoamine oxidase enzyme (MAO), which is bound on the membrane of mitochondria, catalyzes the oxidative deamination of endogenous and exogenous monoamines, including... (Review)
Review
The monoamine oxidase enzyme (MAO), which is bound on the membrane of mitochondria, catalyzes the oxidative deamination of endogenous and exogenous monoamines, including monoamine neurotransmitters such as serotonin, adrenaline, and dopamine. These enzymes have been proven to play a significant role in neurodegeneration; thus, they have recently been researched as prospective therapeutic targets for neurodegenerative illness treatment and management. MAO inhibitors have already been marketed as neurodegeneration illness treatments despite their substantial side effects. Hence, researchers are concentrating on developing novel molecules with selective and reversible inhibitory properties. Piperine, which is a phytochemical component present in black pepper, has been established as a potent MAO inhibitor. Piperine encompasses a piperidine nucleus with antibacterial, anti-inflammatory, antihypertensive, anticonvulsant, antimalarial, antiviral, and anticancer properties. The current Review focuses on the structural changes and structure-activity relationships of piperidine derivatives as MAO inhibitors.
PubMed: 37867639
DOI: 10.1021/acsomega.3c05883