Introduction to Phenelzine
Phenelzine is an irreversible MAO inhibitor, which is thought to act on dopaminergic, serotonergic, & noradrenergic neurons, by inhibiting monoamine oxidase, therefore allowing these neurotransmitters to act both pre & post synaptically to reduce depressive episodes
Using Phenelzine
Effects of Phenelzine
Phenelzine is a non-selective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It inhibits both of the respective isoforms of MAO, MAO-A and MAO-B, and does so almost equally, with slight preference for the former. By inhibiting MAO, phenelzine prevents the breakdown of the monoamine neurotransmitters serotonin, melatonin, norepinephrine, epinephrine, and dopamine, as well as the trace amine neuromodulators such as phenethylamine, tyramine, octopamine, and tryptamine. This leads to an increase in the extracellular concentrations of these neurochemicals and therefore an alteration in neurochemistry and neurotransmission. This action is thought to be the primary mediator in phenelzine's therapeutic benefits.
Chemistry of Phenelzine
Column 1 Column 2 Systematic (IUPAC) name: (2-phenethyl)hydrazine Synonyms: [beta]-phenylethylhydrazine, phenalzine; W-1544a, Nardelzine, Nardil (sulfate) Molecular Formula: C8H12N2 Molar mass: 136.20 g/mol, 234.27 g/mol (sulfate, phenelzine.H2SO4), 172.66 g/mol (hydrochloride) CAS Registry Number: 51-71-8, 156-51-4 (sulfate), 5470-36-0 (hydrochloride) Melting Point: 174°C (hydrochloride) Boiling Point: 74°C @ 0.1 mmHg Flash Point: no data Solubility: sulfate soluble in water Additionnal data: none Notes: freebase aspect : liquid; sulfate : white powder; hydrochloride : crystals
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The Dangers of Phenelzine
The MAOIs are infamous for their problematic food restrictions and drug interactions. Hypertensive crisis may result from the overconsumption of tyramine-containing foods. As a result, patients on phenelzine and other MAOIs must avoid excess quantities of certain foods that contain tyramine such as aged cheeses and cured meats, among others. Serotonin syndrome may result from an interaction with certain drugs which increase serotonin activity such as selective serotonin reuptake inhibitors, serotonin releasing agents, and serotonin agonists. Several deaths have been reported due to drug interaction-related serotonin syndrome such as the case of Libby Zion.
As is the case with other MAOIs, there is a concern regarding phenelzine and the use of both local and general anesthetics. Anyone taking phenelzine should inform their dentist before proceeding with dental surgery, and surgeon in any other contexts.
Phenelzine has also been linked to vitamin B6 deficiency. Transaminases such as GABA-transaminase have been shown to be dependent upon vitamin B6 and may be involved in a potentially related process, since the phenelzine metabolite phenylethylidenehydrazine (PEH) is a GABA transaminase inhibitor. Both phenelzine and vitamin B6 are rendered inactive upon these reactions occurring. For this reason, it may be recommended to supplement with vitamin B6 while taking phenelzine. The pyridoxine form of B6 is recommended for supplementation, since this form has been shown to reduce hydrazine toxicity from phenelzine and, in contrast, the pyridoxal form has been shown to increase the toxicity of hydrazines.