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Journal of Pharmacy Practice Oct 2021The objectives of this manuscript are to describe a case report of a patient whose phenelzine maintenance therapy was discontinued due to concern for a... (Review)
Review
The objectives of this manuscript are to describe a case report of a patient whose phenelzine maintenance therapy was discontinued due to concern for a phenelzine-morphine drug interaction, to review the available literature regarding the potential for this drug-drug interaction, and provide recommendations for this clinical scenario. A PubMed/MEDLINE literature search was conducted and all publications determined to be relevant to this case report were included. Literature describing data, case reports/human studies, and review articles concerning the interaction between morphine and monoamine oxidase inhibitors (MAOIs) were included. A total of 14 publications pertinent to the potential phenelzine-morphine interaction were included in this review including 5 studies, 4 human studies, and 6 review articles detailing the drug interaction profile between opioids and antidepressants. Of these publications, only a single case report of a potential drug interaction between morphine and phenelzine was identified. The literature suggesting a drug interaction between morphine and phenelzine is limited. The combination of phenelzine and morphine, with close monitoring for signs and symptoms of serotonin syndrome, is reasonable for patients with appropriate indications for both agents.
Topics: Analgesics, Opioid; Drug Interactions; Humans; Monoamine Oxidase Inhibitors; Morphine; Pharmaceutical Preparations; Phenelzine
PubMed: 33267714
DOI: 10.1177/0897190020970752 -
ACS Chemical Neuroscience Dec 2023The discovery of monoamine oxidase inhibitors (MAOIs) in the 1950s marked a significant breakthrough in medicine, creating a powerful new category of drug: the... (Review)
Review
The discovery of monoamine oxidase inhibitors (MAOIs) in the 1950s marked a significant breakthrough in medicine, creating a powerful new category of drug: the antidepressant. In the years and decades that followed, MAOIs have been used in the treatment of several pathologies including Parkinson's disease, Alzheimer's disease, and various cancers and as anti-inflammatory agents. Despite once enjoying widespread use, MAOIs have dwindled in popularity due to side effects, food-drug interactions, and the introduction of other antidepressant drug classes such as tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). The recently published prescriber's guide for the use of MAOIs in treating depression has kindled a resurgence of their use in the clinical space. It is therefore timely to review key aspects of the four "classic" MAOIs: high-dose selegiline, isocarboxazid, phenelzine, and tranylcypromine. This review discusses their chemical synthesis, metabolism, pharmacology, adverse effects, and the history and importance of these drugs within the broader field of chemical neuroscience.
Topics: Tranylcypromine; Phenelzine; Isocarboxazid; Selegiline; Antidepressive Agents; Monoamine Oxidase Inhibitors
PubMed: 37966854
DOI: 10.1021/acschemneuro.3c00591 -
Cellular and Molecular Neurobiology Jan 2022Phenelzine (PLZ) is a monoamine oxidase (MAO)-inhibiting antidepressant with anxiolytic properties. This multifaceted drug has a number of pharmacological and... (Review)
Review
Phenelzine (PLZ) is a monoamine oxidase (MAO)-inhibiting antidepressant with anxiolytic properties. This multifaceted drug has a number of pharmacological and neurochemical effects in addition to inhibition of MAO, and findings on these effects have contributed to a body of evidence indicating that PLZ also has neuroprotective/neurorescue properties. These attributes are reviewed in this paper and include catabolism to the active metabolite β-phenylethylidenehydrazine (PEH) and effects of PLZ and PEH on the GABA-glutamate balance in brain, sequestration of reactive aldehydes, and inhibition of primary amine oxidase. Also discussed are the encouraging findings of the effects of PLZ in animal models of stroke, spinal cord injury, traumatic brain injury, and multiple sclerosis, as well other actions such as reduction of nitrative stress, reduction of the effects of a toxin on dopaminergic neurons, potential anticonvulsant actions, and effects on brain-derived neurotrophic factor, neural cell adhesion molecules, an anti-apoptotic factor, and brain levels of ornithine and N-acetylamino acids.
Topics: Animals; Antidepressive Agents; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neuroprotective Agents; Phenelzine; Rats; Rats, Sprague-Dawley
PubMed: 33839994
DOI: 10.1007/s10571-021-01078-3 -
The Australian and New Zealand Journal... Aug 2021
Topics: Humans; Phenelzine
PubMed: 33040569
DOI: 10.1177/0004867420965700 -
La Clinica Terapeutica 2013Monoamine oxidase inhibitors (MAO-I) are the first drugs of antidepressant classes discovered. Phenelzine is a worldwide prescribed MAO-I, studied in a variety of mood... (Review)
Review
Monoamine oxidase inhibitors (MAO-I) are the first drugs of antidepressant classes discovered. Phenelzine is a worldwide prescribed MAO-I, studied in a variety of mood and anxiety disorders. Purpose of the present paper is to critically review the results reported in the scientific international literature focusing on efficacy and safety of phenelzine in clinical psychiatric practice, in order to achieve a better understanding of the relationship between pharmacological data, therapeutic approach and side or adverse effects. We performed a careful PubMed (1980-2012) search on clinical pharmacology and clinical use of phenelzine in various psychiatric disorders. We reported our findings discussing separately clinical pharmacology data and systematic controlled, randomised and not randomised, clinical studies.
Topics: Humans; Mental Disorders; Monoamine Oxidase Inhibitors; Phenelzine; Practice Patterns, Physicians'
PubMed: 23868641
DOI: 10.7417/CT.2013.1571 -
Molecular and Cellular Neurosciences Jun 2023Chemical platforms that facilitate both the identification and elucidation of new areas for therapeutic development are necessary but lacking. Activity-based protein...
Chemical platforms that facilitate both the identification and elucidation of new areas for therapeutic development are necessary but lacking. Activity-based protein profiling (ABPP) leverages active site-directed chemical probes as target discovery tools that resolve activity from expression and immediately marry the targets identified with lead compounds for drug design. However, this approach has traditionally focused on predictable and intrinsic enzyme functionality. Here, we applied our activity-based proteomics discovery platform to map non-encoded and post-translationally acquired enzyme functionalities (e.g. cofactors) in vivo using chemical probes that exploit the nucleophilic hydrazine pharmacophores found in a classic antidepressant drug (e.g. phenelzine, Nardil®). We show the probes are in vivo active and can map proteome-wide tissue-specific target engagement of the drug. In addition to engaging targets (flavoenzymes monoamine oxidase A/B) that are associated with the known therapeutic mechanism as well as several other members of the flavoenzyme family, the probes captured the previously discovered N-terminal glyoxylyl (Glox) group of Secernin-3 (SCRN3) in vivo through a divergent mechanism, indicating this functional feature has biochemical activity in the brain. SCRN3 protein is ubiquitously expressed in the brain, yet gene expression is regulated by inflammatory stimuli. In an inflammatory pain mouse model, behavioral assessment of nociception showed Scrn3 male knockout mice selectively exhibited impaired thermal nociceptive sensitivity. Our study provides a guided workflow to entangle molecular (off)targets and pharmacological mechanisms for therapeutic development.
Topics: Animals; Mice; Male; Phenelzine; Nociception; Proteome; Nerve Tissue Proteins
PubMed: 36924917
DOI: 10.1016/j.mcn.2023.103842 -
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 -
Phenelzine, imipramine, and placebo in borderline patients meeting criteria for atypical depression.Psychopharmacology Bulletin 1989In planning psychopharmacologic treatment of patients with borderline personality disorder (BPD), three partially validated subtypes should be considered. The validity... (Review)
Review
In planning psychopharmacologic treatment of patients with borderline personality disorder (BPD), three partially validated subtypes should be considered. The validity of the schizotypal subtype is supported by their favorable response to neuroleptics as well as by familial and genetic studies. The validity of emotionally unstable character disorder (EUCD) is supported by the presence of neurological soft signs, their negative response to antidepressants, and their positive response to chlorpromazine and lithium. The data presented in this paper suggest that some patients who meet borderline criteria and have atypical depression (patients meeting DSM-III-R criteria for major depression or dysthymia who have reactive mood and any atypical symptoms) clearly benefit from treatment with antidepressant medication. Although some patients with atypical depression who meet borderline criteria will improve with tricyclic therapy, a significantly greater proportion will improve with the monoamine oxidase inhibitor (MAOI), phenelzine.
Topics: Borderline Personality Disorder; Humans; Imipramine; Phenelzine; Placebos
PubMed: 2698483
DOI: No ID Found -
Anaesthesia Jan 1986A 46-year-old female with severe phenelzine poisoning was managed successfully by alpha blockade and fluid loading, with the aid of invasive haemodynamic monitoring. The...
A 46-year-old female with severe phenelzine poisoning was managed successfully by alpha blockade and fluid loading, with the aid of invasive haemodynamic monitoring. The pathophysiology was documented, showing elevated plasma and urinary catecholamines, cardiovascular abnormalities and a contracted blood volume. Most of these changes were reversed following treatment.
Topics: Adrenergic alpha-Antagonists; Catecholamines; Critical Care; Female; Fluid Therapy; Hemodynamics; Humans; Middle Aged; Monitoring, Physiologic; Phenelzine
PubMed: 2868672
DOI: 10.1111/j.1365-2044.1986.tb12704.x -
American Journal of Hospital Pharmacy Jun 1979
Topics: Adult; Beverages; Caffeine; Carbonated Beverages; Drug Interactions; Female; Headache; Humans; Hypertension; Phenelzine
PubMed: 463881
DOI: No ID Found