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Anesthesia Progress 2017Millions of patients take antidepressant medications in the United States for the treatment of depression or anxiety disorders. Some antidepressants are prescribed... (Review)
Review
Millions of patients take antidepressant medications in the United States for the treatment of depression or anxiety disorders. Some antidepressants are prescribed off-label to treat problems such as chronic pain, low energy, and menstrual symptoms. Antidepressants are a broad and expansive group of medications, but the more common drug classes include tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and monoamine oxidase inhibitors. A miscellaneous or "atypical" category covers other agents. Some herbal supplements that claim to have antidepressant activity will also be discussed. In Part I of this review, antidepressant pharmacology, adverse effects, and drug interactions with adrenergic agonists will be discussed. In part II, drug interactions with sedation and general anesthetics will be reviewed. Bleeding effects and serotonin syndrome implications in anesthetic practice will also be highlighted.
Topics: Adrenergic Agonists; Anesthetics; Animals; Antidepressive Agents; Dietary Supplements; Drug Interactions; Humans; United States
PubMed: 29200376
DOI: 10.2344/anpr-64-04-14 -
Frontiers in Bioscience (Landmark... Jan 2017The cortico-striatal network plays a major role in executive functions (EF), and is believed to play a role in the pathophysiology of Parkinson's disease (PD). However,... (Review)
Review
The cortico-striatal network plays a major role in executive functions (EF), and is believed to play a role in the pathophysiology of Parkinson's disease (PD). However, the tools to assess EF are limited. This review assesses the impact of all PD interventions, namely, pharmacotherapy, physical exercise and Deep Brain Stimulation (DBS) surgery on EF. The effect of PD pharmacotherapy varies with the drug class, neuropsychological test used and the affected dopamine receptor family. There appears to be a benefit of aerobic exercise on EF, including judgment and attention. The effect of Deep Brain Stimulation on EF might vary with site of brain stimulation, the neuropsychological test performed and the pre-operative cognitive state. The effect of EF on underlying manifestations and as a factor in the pathway to the motor benefit needs to be better assessed with more accurate tests that focus on motor component of EF.
Topics: Antiparkinson Agents; Catechol O-Methyltransferase Inhibitors; Deep Brain Stimulation; Dopamine Agonists; Executive Function; Exercise Therapy; Humans; Levodopa; Monoamine Oxidase Inhibitors; Parkinson Disease
PubMed: 27814622
DOI: 10.2741/4492 -
International Journal of Molecular... Aug 2023Selegiline and rasagiline are two selective monoamine oxidase B (MAO-B) inhibitors used in the treatment of Parkinson's disease. In their clinical application, however,...
Selegiline and rasagiline are two selective monoamine oxidase B (MAO-B) inhibitors used in the treatment of Parkinson's disease. In their clinical application, however, differences in L-dopa-sparing potencies have been observed. The aim of this study was to find neurochemical and behavioral explanations for the antiparkinsonian effects of these drugs. We found that selegiline possesses a dopaminergic enhancer effect: it stimulated the electrically induced [H]dopamine release without influencing the resting [H]dopamine release from rat striatal slices in 10-10 mol/L concentrations. Rasagiline added in 10 to 10 mol/L concentrations did not alter the resting or electrically stimulated [H]dopamine release. Rasagiline (10 mol/L), however, suspended the stimulatory effect of selegiline on the electrically induced [H]dopamine release. The trace amine-associated receptor 1 (TAAR1) antagonist EPPTB (10-10 mol/L) also inhibited the stimulatory effect of selegiline on [H]dopamine release. The effect of selegiline in its enhancer dose (5.33 nmol/kg) against tetrabenazine-induced learning deficit measured in a shuttle box apparatus was abolished by a 5.84 nmol/kg dose of rasagiline. The selegiline metabolite (-)methamphetamine (10 mol/L) also exhibited enhancer activity on [H]dopamine release. We have concluded that selegiline acts as an MAO-B inhibitor and a dopaminergic enhancer drug, and the latter relates to an agonist effect on TAAR1. In contrast, rasagiline is devoid of enhancer activity but may act as an antagonist on TAAR1.
Topics: Animals; Rats; Selegiline; Dopamine; Indans; Monoamine Oxidase
PubMed: 37686140
DOI: 10.3390/ijms241713334 -
Chemico-biological Interactions May 2019Phenelzine (β-phenylethylhydrazine) is a monoamine oxidase (MAO)-inhibiting antidepressant with anxiolytic properties. It possesses a number of important... (Review)
Review
Phenelzine (β-phenylethylhydrazine) is a monoamine oxidase (MAO)-inhibiting antidepressant with anxiolytic properties. It possesses a number of important pharmacological properties which may alter the effects of oxidative stress. After conducting a comprehensive literature search, the authors of this review paper aim to provide an overview and discussion of the mechanisms by which phenelzine may attenuate oxidative stress. It inhibits γ-aminobutyric acid (GABA) transaminase, resulting in elevated brain GABA levels, inhibits both MAO and primary amine oxidase and, due to its hydrazine-containing structure, reacts chemically to sequester a number of reactive aldehydes (e.g. acrolein and 4-hydroxy-2-nonenal) proposed to be implicated in oxidative stress in a number of neurodegenerative disorders. Phenelzine is unusual in that it is both an inhibitor of and a substrate for MAO, the latter action producing at least one active metabolite, β-phenylethylidenehydrazine (PEH). This metabolite inhibits GABA transaminase, is a very weak inhibitor of MAO but a strong inhibitor of primary amine oxidase, and sequesters aldehydes. Phenelzine may ameliorate the effects of oxidative stress by reducing formation of reactive metabolites (aldehydes, hydrogen peroxide, ammonia/ammonia derivatives) produced by the interaction of MAO with biogenic amines, by sequestering various other reactive aldehydes and by inhibiting primary amine oxidase. In PC12 cells treated with the neurotoxin MPP, phenelzine has been reported to reduce several adverse effects of MPP. It has also been reported to reduce lipid peroxidative damage induced in plasma and platelet proteins by peroxynitrite. In animal models, phenelzine has a neuroprotective effect in global ischemia and in cortical impact traumatic brain injury. Recent studies reported in the literature on the possible involvement of acrolein in spinal cord injury and multiple sclerosis indicate that phenelzine can attenuate adverse effects of acrolein in these models. Results from studies in our laboratories on effects of phenelzine and PEH on primary amine oxidase (which catalyzes formation of toxic aldehydes and is overexpressed in Alzheimer's disease), on sequestration of the toxic aldehyde acrolein, and on reduction of acrolein-induced toxicity in mouse cortical neurons are also reported.
Topics: Animals; Antidepressive Agents; Free Radical Scavengers; Humans; Molecular Structure; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Oxidative Stress; Phenelzine
PubMed: 30857888
DOI: 10.1016/j.cbi.2019.03.003 -
Journal of Microbiology and... Jul 2021Three compounds were isolated from marine-derived sp. CNQ-031, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE),...
Three compounds were isolated from marine-derived sp. CNQ-031, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE-1) were evaluated. Compound 1 (5,7-dihydroxy-2-isopropyl-4H-chromen-4-one) was a potent and selective inhibitor of MAO-A, with a 50% inhibitory concentration (IC) of 2.70 μM and a selectivity index (SI) of 10.0 versus MAO-B. Compound 2 [5,7-dihydroxy-2-(1-methylpropyl)-4H-chromen-4-one] was a potent and low-selective inhibitor of MAO-B, with an IC of 3.42 μM and an SI value of 2.02 versus MAO-A. Compound 3 (1-methoxyphenazine) did not inhibit MAO-A or MAO-B. All three compounds showed little inhibitory activity against AChE, BChE, and BACE-1. The K value of compound 1 for MAO-A was 0.94 ± 0.28 μM, and the K values of compound 2 for MAO-A and MAO-B were 3.57 ± 0.60 and 1.89 ± 0.014 μM, respectively, with competitive inhibition. The 1-methylpropyl group in compound 2 increased the MAO-B inhibitory activity compared with the isopropyl group in compound 1. Inhibition of MAO-A and MAO-B by compounds 1 and 2 was recovered by dialysis experiments. These results suggest that compounds 1 and 2 are reversible, competitive inhibitors of MAOs and can be considered potential therapies for neurological disorders such as depression and Alzheimer's disease.
Topics: Animals; Chromones; Geologic Sediments; Humans; Inhibitory Concentration 50; Kinetics; Molecular Structure; Monoamine Oxidase Inhibitors; Seawater; Streptomyces
PubMed: 34099598
DOI: 10.4014/jmb.2105.05003 -
European Journal of Medicinal Chemistry Mar 2024Monoamine oxidases A and B (MAO A, B) are ubiquitous enzymes responsible for oxidative deamination of amine neurotransmitters and xenobiotics. Despite decades of... (Review)
Review
Monoamine oxidases A and B (MAO A, B) are ubiquitous enzymes responsible for oxidative deamination of amine neurotransmitters and xenobiotics. Despite decades of studies, MAO inhibitors (MAOIs) find today limited therapeutic space as second-line drugs for the treatment of depression and Parkinson's disease. In recent years, a renewed interest in MAOIs has been raised up by several studies investigating the role of MAOs, particularly MAO A, in tumor insurgence and progression, and the efficacy of MAOIs as coadjutants in the therapy of chemoresistant tumors. In this survey, we highlight the implication of MAOs in the biochemical pathways of tumorigenesis and review the state-of-the-art of preclinical and clinical studies of MAOIs as anticancer agents used in monotherapy or in combination with antitumor chemotherapeutics.
Topics: Humans; Monoamine Oxidase Inhibitors; Monoamine Oxidase; Parkinson Disease
PubMed: 38290352
DOI: 10.1016/j.ejmech.2024.116180 -
International Journal of Molecular... Apr 2020Multiple system atrophy (MSA) is a rare, severe, and rapidly progressive neurodegenerative disorder categorized as an atypical parkinsonian syndrome. With a mean life... (Review)
Review
Multiple system atrophy (MSA) is a rare, severe, and rapidly progressive neurodegenerative disorder categorized as an atypical parkinsonian syndrome. With a mean life expectancy of 6-9 years after diagnosis, MSA is clinically characterized by parkinsonism, cerebellar ataxia, autonomic failure, and poor l-Dopa responsiveness. Aside from limited symptomatic treatment, there is currently no disease-modifying therapy available. Consequently, distinct pharmacological targets have been explored and investigated in clinical studies based on MSA-related symptoms and pathomechanisms. Parkinsonism, cerebellar ataxia, and autonomic failure are the most important symptoms targeted by symptomatic treatments in current clinical trials. The most prominent pathological hallmark is oligodendroglial cytoplasmic inclusions containing alpha-synuclein, thus classifying MSA as synucleinopathy. Additionally, myelin and neuronal loss accompanied by micro- and astrogliosis are further distinctive features of MSA-related neuropathology present in numerous brain regions. Besides summarizing current symptomatic treatment strategies in MSA, this review critically reflects upon potential cellular targets and disease-modifying approaches for MSA such as (I) targeting α-syn pathology, (II) intervening neuroinflammation, and (III) neuronal loss. Although these single compound trials are aiming to interfere with distinct pathogenetic steps in MSA, a combined approach may be necessary to slow down the rapid progression of the oligodendroglial associated synucleinopathy.
Topics: Adrenergic alpha-1 Receptor Agonists; Animals; Disease Models, Animal; Humans; Induced Pluripotent Stem Cells; Monoamine Oxidase Inhibitors; Multiple System Atrophy; Neuroglia; Peroxidase; alpha-Synuclein
PubMed: 32316335
DOI: 10.3390/ijms21082775 -
Molecules (Basel, Switzerland) Mar 2023Monoamine oxidase (MAO) oxidizes neurotransmitters and xenobiotic amines, including vasopressor and neurotoxic amines such as the MPTP neurotoxin. Its inhibitors are...
Monoamine oxidase (MAO) oxidizes neurotransmitters and xenobiotic amines, including vasopressor and neurotoxic amines such as the MPTP neurotoxin. Its inhibitors are useful as antidepressants and neuroprotectants. This work shows that diluted soy sauce (1/3) and soy sauce extracts inhibited human MAO-A and -B isozymes in vitro, which were measured with a chromatographic assay to avoid interferences, and it suggests the presence of MAO inhibitors. Chromatographic and spectrometric studies showed the occurrence of the β-carboline alkaloids harman and norharman in soy sauce extracts inhibiting MAO-A. Harman was isolated from soy sauce, and it was a potent and competitive inhibitor of MAO-A (0.4 µM, 44 % inhibition). The concentrations of harman and norharman were determined in commercial soy sauces, reaching 243 and 52 μg/L, respectively. Subsequently, the alkaloids 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (THCA) and 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (MTCA) were identified and analyzed in soy sauces reaching concentrations of 69 and 448 mg/L, respectively. The results show that MTCA was a precursor of harman under oxidative and heating conditions, and soy sauces increased the amount of harman under those conditions. This work shows that soy sauce contains bioactive β-carbolines and constitutes a dietary source of MAO-A and -B inhibitors.
Topics: Humans; Soy Foods; Carbolines; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Alkaloids; Plant Extracts; Amines
PubMed: 36985694
DOI: 10.3390/molecules28062723 -
International Journal of Molecular... Nov 2022Serotonin (5-HT) plays an essential role in regulating female reproductive function in many animals. 5-HT accumulates in the mammalian ovary with the involvement of...
Serotonin (5-HT) plays an essential role in regulating female reproductive function in many animals. 5-HT accumulates in the mammalian ovary with the involvement of membrane serotonin transporter SERT and is functionally active in the oocytes of growing follicles, but shows almost no activity in follicular cells. In this study, we clarified the interplay between 5-HT membrane transport and its degradation by monoamine oxidase (MAO) in the mammalian ovary. Using pharmacologic agents and immunohistochemical staining of the cryosections of ovaries after serotonin administration in vitro, we demonstrated the activity of transport and degradation systems in ovarian follicles. The MAO inhibitor pargyline increased serotonin accumulation in the granulosa cells of growing follicles, indicating the activity of both serotonin uptake and degradation by MAO in these cells. The activity of MAO and the specificity of the membrane transport of serotonin was confirmed in primary granulosa cell culture treated with pargyline and fluoxetine. Moreover, the accumulation of serotonin is more effective in the denuded oocytes and occurs at lower concentrations than in the oocytes within the follicles. This confirms that the activity of SERT and MAO in the granulosa cells surrounding the oocytes impedes the accumulation of serotonin in the oocytes and forms a functional barrier to serotonin.
Topics: Animals; Mice; Female; Serotonin; Granulosa Cells; Ovarian Follicle; Oocytes; Monoamine Oxidase; Serotonin Plasma Membrane Transport Proteins; Pargyline; Mammals
PubMed: 36499156
DOI: 10.3390/ijms232314828 -
International Journal of Molecular... Jan 2023Parkinson's disease (PD) is the second most common neurodegenerative disease in older individuals worldwide. Pharmacological treatment for such a disease consists of...
Parkinson's disease (PD) is the second most common neurodegenerative disease in older individuals worldwide. Pharmacological treatment for such a disease consists of drugs such as monoamine oxidase B (MAO-B) inhibitors to increase dopamine concentration in the brain. However, such drugs have adverse reactions that limit their use for extended periods; thus, the design of less toxic and more efficient compounds may be explored. In this context, cheminformatics and computational chemistry have recently contributed to developing new drugs and the search for new therapeutic targets. Therefore, through a data-driven approach, we used cheminformatic tools to find and optimize novel compounds with pharmacological activity against MAO-B for treating PD. First, we retrieved from the literature 3316 original articles published between 2015-2021 that experimentally tested 215 natural compounds against PD. From such compounds, we built a pharmacological network that showed rosmarinic acid, chrysin, naringenin, and cordycepin as the most connected nodes of the network. From such compounds, we performed fingerprinting analysis and developed evolutionary libraries to obtain novel derived structures. We filtered these compounds through a docking test against MAO-B and obtained five derived compounds with higher affinity and lead likeness potential. Then we evaluated its antioxidant and pharmacokinetic potential through a docking analysis (NADPH oxidase and CYP450) and physiologically-based pharmacokinetic (PBPK modeling). Interestingly, only one compound showed dual activity (antioxidant and MAO-B inhibitors) and pharmacokinetic potential to be considered a possible candidate for PD treatment and further experimental analysis.
Topics: Humans; Aged; Parkinson Disease; Monoamine Oxidase Inhibitors; Structure-Activity Relationship; Neurodegenerative Diseases; Antioxidants; Monoamine Oxidase
PubMed: 36674652
DOI: 10.3390/ijms24021134