Moclobemide for depressive disorder

Moclobemide

Small Molecule

Approved

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

For the treatment of depression.

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.

The mechanism of action of moclobemide involves the selective, reversible inhibition of MAO-A. This inhibition leads to a decrease in the metabolism and destruction of monoamines in the neurotransmitters. This results in an increase in the monoamines, relieving depressive symptoms.

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.