化合物信息

Drug Groups

approved

Description

An irreversible non-selective inhibitor of monoamine oxidase. May be used to treat major depressive disorder.

Indication

For the treatment of major depressive disorder. Has also been used with some success in the management of bulimia nervosa.

Pharmacology

Phenelzine belongs to a class of antidepressants called monoamine oxidase inhibitors (MAOIs). MAO is an enzyme that catalyzes the oxidative deamination of a number of amines, including serotonin, norepinephrine, epinephrine, and dopamine. Two isoforms of MAO, A and B, are found in the body. MAO-A is mainly found within cells located in the periphery and catalyzes the breakdown of serotonin, norepinephrine, epinephrine, dopamine and tyramine. MAO-B acts on phenylethylamine, norepinephrine, epinephrine, dopamine and tyramine, is localized extracellularly and is found predominantly in the brain. While the mechanism of MAOIs is still unclear, it is thought that they act by increasing free serotonin and norepinephrine concentrations and/or by altering the concentrations of other amines in the CNS. It has been postulated that depression is caused by low levels of serotonin and/or norepinephrine and that increasing serotonergic and norepinephrinergic neurotransmission results in relief of depressive symptoms. MAO A inhibition is thought to be more relevant to antidepressant activity than MAO B inhibition. Selective MAO B inhibitors, such as selegiline, have no antidepressant effects. Response to therapy generally occurs 2 - 4 weeks following onset though some patients may not experience symptom relief for up to 8 weeks.

Toxicity

Symptoms of overdose include drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, trismus, opisthotonos, convulsions and coma, rapid and irregular pulse, hypertension, hypotension and vascular collapse, precordial pain, respiratory depression and failure, hyperpyrexia, diaphoresis, and cool, clammy skin. Hypertensive crisis may occur with the ingestion of tyramine-rich foods such as cured meats, poultry or fish, aged cheeses, concentrated soy products, tap beer and wine, yeast extracts, broad bean pods and fava beans and sauerkraut.

Affected Organisms

Biotransformation

Hepatic. Acetylation of phenelzine appears to be a minor metabolic pathway. Beta-phenylethylamine is a metabolite of phenelzine, and there is indirect evidence that phenelzine may also be ring-hydroxylated and N-methylated.

Absorption

Readily absorbed after oral administration.

Half Life

1.2-11.6 hours following single dose administration. Multiple-dose pharmacokinetics have not been studied.

Elimination

NARDIL ? is extensively metabolized, primarily by oxidation via monoamine oxidase.

References

External Links