Metabolism of monoamine oxidase inhibitors.

ABSTRACT

1. Despite the fact that monoamine oxidase inhibitors have been used clinically and in animal experiments for many years, much still remains unknown about their metabolism. An overview of the metabolic aspects of several monoamine oxidase inhibitors, including phenelzine, tranylcypromine, pheniprazine, pargyline and deprenyl, is presented. 2. There is still considerable controversy surrounding the role of acetylation in the metabolism of phenelzine. The possibility of ring hydroxylation as well as the formation of beta-phenylethylamine, phenylacetic acid and rho-hydroxyphenylacetic acid from phenelzine is explored. 3. Tranylcypromine has been shown to undergo acetylation and ring hydroxylation. Opening of the cyclopropyl ring is also possible, although this still remains a matter of debate. The pharmacological activity and pharmacokinetic properties of the enantiomers of tranylcypromine are discussed. Chemical substitution in the 4-position of the phenyl ring has been utilized in the design of tranylcypromine analogues with potential antidepressant activity. 4. The formation of amphetamine from pheniprazine and the metabolism of the N-propargyl drugs pargyline and deprenyl are discussed.