Pharmacokinetics of monoamine oxidase inhibitors.

Few studies on the pharmacokinetics and plasma drug levels of monoamine oxidase (MAO) inhibitors have been performed, despite several decades of clinical use. Older MAO inhibitors such as tranylcypromine produce neuronal accumulation of neurotransmitter amines as a consequence of functionally irreversible MAO inhibition. Typically, these agents are cleared from the body rapidly, so plasma drug levels are not correlated with MAO inhibition. However, recent research has demonstrated that tranylcypromine can produce direct and reversible pharmacologic effects, as well as clinical mood effects, that appear more closely related to transient plasma tranylcypromine levels than to the degree of MAO inhibition. In addition, a new generation of reversible MAO inhibitors is now being introduced. The antidepressant actions of these latter agents will almost certainly be directly influenced by pharmacokinetic factors. This review summarizes the existing pharmacokinetic literature on tranylcypromine, phenelzine, moclobemide, and selegiline. These drugs and others like them promise to become increasingly important in modern psychopharmacologic practice.