化合物信息

Drug Groups

approved

Description

A reversible monoamine oxidase inhibitor (MAOI) selective for isoform A (RIMA) used to treat major depressive disorder.

Indication

For the treatment of depression.

Pharmacology

Moclobemide belongs to a class of MAOI antidepressants known as reversible inhibitors of monoamine oxidase type-A (RIMAs). The primary role of monoamine oxidase MAO lies in the metabolism of and regulation of the levels of monoamines (serotonin, norepinephrine, and dopamine). Within neurons, MAO appears to regulate the levels of monoamines released upon synaptic firing. Since depression is associated with low levels of monoamines, the inhibition of MAO serves to ease depressive symptoms. RIMAs demonstrate transient inhibition of the substrate binding site of MAO-A as well as competitive displacement from this site by bioamines. The RIMAs are distinguished from the older monoamine oxidase inhibitors (MAOIs) by their selectivity and reversibility.

Toxicity

LD50 (mouse) is 730mg/kg and LD50 (rat) is 1,300mg/kg. Signs of toxicity include hypertension, drowsiness, dizziness, confusion, tremors, headache, agitation, muscle rigidity and seizures.

Affected Organisms

Biotransformation

Moclobemide is almost completely metabolized in the liver by Cytochrome P450 2C19 and 2D6.

Absorption

Well absorbed from the gastrointestinal tract (> 95%). The presence of food reduces the rate but not the extent of absorption. Hepatic first pass metabolism reduces bioavailability to 45-70% following administration of a single dose, but increases to 80% with multiple dosing as a result of saturation of the first pass effect. Peak plasma concentrations are reached within 1 - 2 hours following oral administration.

Half Life

1-2 hours (4 hours in cirrhotic patients); metabolites are renally excreted

Protein Binding

Approximately 50% (primarily to albumin)

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