Moclobemide is a reversible inhibitor of monoamine oxidase A (RIMA, a type of monoamine oxidase inhibitor (MAOI)) and acts on epinephrine (adrenaline), norepinephrine (noradrenaline), serotonin, and dopamine. Unlike standard MAOIs, possible side-effects do not include cardiovascular complications (hypertension) with encephalopathy, liver toxicity or hyperthermia. However, moclobemide's therapeutic effects only last for a short period of time.

A single 300mg dose of moclobemide inhibits 80% of monoamine oxidase A (MAO-A) and 30% of monoamine oxidase B (MAO-B), blocking the decomposition of norepinephrine, serotonin and, to a lesser extent, dopamine. No reuptake inhibition on any of the neurotransmitters occurs. The pharmacodynamic action encompasses activation, elevation of mood, and improvement of symptoms like dysphoria, fatigue, and difficulties in concentration. The duration and quality of sleep may be improved. In the treatment of depression the antidepressant effect often becomes evident in the first week of therapy (earlier as noted with TCAs/SSRIs).

If the therapy has to be switched from Moclobemide to a TCA or another antidepressant, the treatment with the new agent can be started the next day (without latent period) due to the short-lived effects of Moclobemide.

Pharmacokinetics

Moclobemide is rapidly absorbed. Peak plasma levels occur 0.3 to 2 hours after oral administration. The bioavailability increases during the first week of therapy from 60% to 80% and more. The elimination half-life is 2 to 4 hours. Despite its short half-life the pharmacodynamic action of a single dose persists for approximately 16 hours. The drug is almost completely metabolized in the liver by 2 CYP-Enzymes (CYP450 2C19, Mephenytoin-Polymorphism, and CYP450 2D6, Debrisoquin-Polymorphism). Main metabolites are a lactam and a n-oxid; active metabolites are found only in trace amounts. The unchanged drug (less than 1%) as well as the metabolites are excreted renally (in urine).

Animal Toxicology

Acute Toxicity : The oral LD50-values in mouse and rat are quite high, indicating a wide therapeutic index. LD50 (mouse) is 730mg/kg and LD50 (rat) is 1,300mg/kg. In dogs doses in exceed of 300mg/kg led to vomiting, salivation, ataxia, and drowsiness.
Chronic Toxicity : In a 18-months-study in rats with 10mg/kg no signs of chronic toxicity were noted, with 50mg/kg and 250mg/kg only a slight loss of weight, and with 250mg/kg mildly elevated Alkaline Phosphatase and Gamma-GT. Studies in dogs revealed no toxicity relevant for humans. No evidence for a possible hepatic or cardiovascular toxicity was found.