Selective inhibitors of monoamine oxidase. 3. Structure-activity relationship of tricyclics bearing imidazoline, oxadiazole, or tetrazole groups

Abstract

Inhibition of monoamine oxidase A (MAO A) is believed to cause antidepressant and possibly antianxiety effects. The previous paper had developed structure-activity relationships (SAR) for in vitro MAO A inhibition by tricyclic N-arylamides. It is shown in this paper that the same in vitro SAR can be carried over to tricyclics whose potentially toxic amide function is replaced by an appropriately substituted imidazoline, a 1,2,4- or 1,3,4-oxadiazole, or an alkylated tetrazole moiety. Dialysis of the inhibitor from the enzyme was used as a measure of reversibility which correlates with a low ability to cause a blood pressure rise with ingested tyramine ("cheese effect").