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European Journal of Clinical... Dec 2020To investigate the comparative effectiveness of dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors available for treatment of Parkinson's disease. (Comparative Study)
Comparative Study Meta-Analysis
PURPOSE
To investigate the comparative effectiveness of dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors available for treatment of Parkinson's disease.
METHODS
We performed a systematic literature search identifying randomized controlled trials investigating 4 dopamine agonists (cabergoline, pramipexole, ropinirole, rotigotine) and 3 MAO-B inhibitors (selegiline, rasagiline, safinamide) for Parkinson's disease. We extracted and pooled data from included clinical trials in a joint model allowing both direct and indirect comparison of the seven drugs. We considered dopamine agonists and MAO-B inhibitors given as monotherapy or in combination with levodopa. Selected endpoints were change in the Unified Parkinson's Disease Rating Scale (UPDRS) score, serious adverse events and withdrawals. We estimated the relative effectiveness of each dopamine agonist and MAO-B inhibitor versus comparator drug.
RESULTS
Altogether, 79 publications were included in the analysis. We found all the investigated drugs to be effective compared with placebo when given as monotherapy except safinamide. When considering combination treatment, the estimated relative effects of selegiline, pramipexole, ropinirole, rotigotine, cabergoline, rasagiline and safinamide were 2.316 (1.819, 2.951), 2.091 (1.889, 2.317), 2.037 (1.804, 2.294), 1.912 (1.716, 2.129), 1.664 (1.113, 2.418), 1.584 (1.379, 1.820) and 1.179 (1.031, 1.352), respectively, compared with joint placebo and levodopa treatment.
CONCLUSIONS
Dopamine agonists were found to be effective as treatment for Parkinson's disease, both when given as monotherapy and in combination with levodopa. Selegiline and rasagiline were also found to be effective for treating Parkinson's disease, and selegiline was the best option in combination with levodopa among all the drugs investigated.
Topics: Dopamine Agonists; Drug Therapy, Combination; Humans; Indans; Levodopa; Monoamine Oxidase Inhibitors; Parkinson Disease; Randomized Controlled Trials as Topic; Selegiline; Treatment Outcome
PubMed: 32710141
DOI: 10.1007/s00228-020-02961-6 -
Pharmacotherapy Apr 2015Treatment-resistant depression (TRD) is a major health concern. More than 40% of patients treated for major depressive disorder with an appropriate antidepressant dose... (Review)
Review
Treatment-resistant depression (TRD) is a major health concern. More than 40% of patients treated for major depressive disorder with an appropriate antidepressant dose for an adequate duration fail to respond. Further, approximately half of adults with major depressive disorder fail to achieve sustained remission despite various medication trials. The utilization of monoamine oxidase inhibitors (MAOIs) for the treatment of depression in clinical practice today is low due to their widely known adverse effects, some of which may be life threatening, and the risk for dietary and drug interactions. For these reasons, MAOIs are not recommended to be prescribed along with other antidepressants or certain prescription or nonprescription drugs. Pharmacologic options are limited for individuals with TRD, however, and there is a paucity of data on the efficacy of MAOIs in combination with other antidepressants for the management of TRD. We performed a search of the PubMed database (inception through January 25, 2015) to identify cases that illustrate the potential utility, as well as risks, of combination treatment with MAOIs and other antidepressants for the management of TRD; 18 articles met the criteria for our search. In addition, we performed a retrospective case series by reviewing the medical records of 29 adults treated for depression with an MAOI plus another psychotropic agent (an antidepressant or stimulant medication) between 2003 and 2012 at a large Midwestern teaching hospital. We compared the findings of the published experience with our local experience to allow for more informed decisions regarding pharmacotherapy in patients with TRD. We separated the local experience into two groups: 15 cases with the selective MAO type B inhibitor selegiline combined with medications presumed to increase the risk of serotonin syndrome and 14 cases with nonselective MAOIs (phenelzine and tranylcypromine) combined with other contraindicated medications. Although risks of combination treatment certainly exist with selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, or clomipramine, the current literature supports cautious use of combining MAOIs with other antidepressants in patients with TRD who have failed multiple treatment modalities. In addition, the data from the 29 patients receiving combination therapy with an MAOI and another antidepressant or stimulant medication revealed that 21% improved significantly, with no complications. This case series and literature review suggest that when used under close supervision and under the care of an experienced clinician in psychiatry, combination therapy may be a consideration for the management of TRD in patients not responding to monotherapy or other combinations of antidepressants.
Topics: Antidepressive Agents; Central Nervous System Stimulants; Contraindications; Depression; Depressive Disorder, Major; Drug Interactions; Drug Therapy, Combination; Humans; Monoamine Oxidase Inhibitors; Treatment Failure
PubMed: 25884531
DOI: 10.1002/phar.1576 -
Nature Oct 2017Catecholamine-induced lipolysis, the first step in the generation of energy substrates by the hydrolysis of triglycerides, declines with age. The defect in the...
Catecholamine-induced lipolysis, the first step in the generation of energy substrates by the hydrolysis of triglycerides, declines with age. The defect in the mobilization of free fatty acids in the elderly is accompanied by increased visceral adiposity, lower exercise capacity, failure to maintain core body temperature during cold stress, and reduced ability to survive starvation. Although catecholamine signalling in adipocytes is normal in the elderly, how lipolysis is impaired in ageing remains unknown. Here we show that adipose tissue macrophages regulate the age-related reduction in adipocyte lipolysis in mice by lowering the bioavailability of noradrenaline. Unexpectedly, unbiased whole-transcriptome analyses of adipose macrophages revealed that ageing upregulates genes that control catecholamine degradation in an NLRP3 inflammasome-dependent manner. Deletion of NLRP3 in ageing restored catecholamine-induced lipolysis by downregulating growth differentiation factor-3 (GDF3) and monoamine oxidase A (MAOA) that is known to degrade noradrenaline. Consistent with this, deletion of GDF3 in inflammasome-activated macrophages improved lipolysis by decreasing levels of MAOA and caspase-1. Furthermore, inhibition of MAOA reversed the age-related reduction in noradrenaline concentration in adipose tissue, and restored lipolysis with increased levels of the key lipolytic enzymes adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL). Our study reveals that targeting neuro-immunometabolic signalling between the sympathetic nervous system and macrophages may offer new approaches to mitigate chronic inflammation-induced metabolic impairment and functional decline.
Topics: Adipocytes; Adipose Tissue; Aging; Animals; Caspase 1; Catecholamines; Gene Expression Profiling; Gene Expression Regulation; Growth Differentiation Factor 3; Inflammasomes; Lipase; Lipolysis; Macrophages; Mice; Monoamine Oxidase; Monoamine Oxidase Inhibitors; NLR Family, Pyrin Domain-Containing 3 Protein; Norepinephrine; Sterol Esterase
PubMed: 28953873
DOI: 10.1038/nature24022 -
Nature Medicine Aug 2014In Alzheimer's disease (AD), memory impairment is the most prominent feature that afflicts patients and their families. Although reactive astrocytes have been observed...
In Alzheimer's disease (AD), memory impairment is the most prominent feature that afflicts patients and their families. Although reactive astrocytes have been observed around amyloid plaques since the disease was first described, their role in memory impairment has been poorly understood. Here, we show that reactive astrocytes aberrantly and abundantly produce the inhibitory gliotransmitter GABA by monoamine oxidase-B (Maob) and abnormally release GABA through the bestrophin 1 channel. In the dentate gyrus of mouse models of AD, the released GABA reduces spike probability of granule cells by acting on presynaptic GABA receptors. Suppressing GABA production or release from reactive astrocytes fully restores the impaired spike probability, synaptic plasticity, and learning and memory in the mice. In the postmortem brain of individuals with AD, astrocytic GABA and MAOB are significantly upregulated. We propose that selective inhibition of astrocytic GABA synthesis or release may serve as an effective therapeutic strategy for treating memory impairment in AD.
Topics: Alzheimer Disease; Amyloid Precursor Protein Secretases; Amyloid beta-Peptides; Animals; Astrocytes; Bestrophins; Cerebellum; Dentate Gyrus; Disease Models, Animal; Eye Proteins; GABA Antagonists; Hippocampus; Humans; Ion Channels; Male; Maze Learning; Memory; Memory Disorders; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Transgenic; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Peptide Fragments; Plaque, Amyloid; Putrescine; RNA, Small Interfering; Receptors, GABA; gamma-Aminobutyric Acid
PubMed: 24973918
DOI: 10.1038/nm.3639 -
Journal of Neural Transmission (Vienna,... May 2020Monoamine oxidase B (MAO-B) inhibitors have an established role in the treatment of Parkinson's disease as monotherapy or adjuvant to levodopa. Two major recognitions... (Review)
Review
Monoamine oxidase B (MAO-B) inhibitors have an established role in the treatment of Parkinson's disease as monotherapy or adjuvant to levodopa. Two major recognitions were required for their introduction into this therapeutic field. The first was the elucidation of the novel pharmacological properties of selegiline as a selective MAO-B inhibitor by Knoll and Magyar and the original idea of Riederer and Youdim, supported by Birkmayer, to explore its effect in parkinsonian patients with on-off phases. In the 1960s, MAO inhibitors were mainly studied as potential antidepressants, but Birkmayer found that combined use of levodopa and various MAO inhibitors improved akinesia in Parkinson's disease. However, the serious side effects of the first non-selective MAO inhibitors prevented their further use. Later studies demonstrated that MAO-B, mainly located in glial cells, is important for dopamine metabolism in the brain. Recently, cell and molecular studies revealed interesting properties of selegiline opening new possibilities for neuroprotective mechanisms and a disease-modifying effect of MAO-B inhibitors.
Topics: Animals; Humans; Monoamine Oxidase Inhibitors; Neuroprotective Agents; Parkinson Disease; Selegiline
PubMed: 31562557
DOI: 10.1007/s00702-019-02082-0 -
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