Comparative effects of dehydropirlindole and other compounds on rat brain monoamine oxidase type A

Dehydropirlindole (DHP) is the dehydroderivative of pirlindole, a short-acting inhibitor of monoamine oxidase type A (MAO-A). DHP would be formed in vivo from oxidation of pirlindole by MAO-A. The aim of this work is to compare the inhibitory potency of DHP with three reference compounds: harmaline, befloxatone and clorgyline; the two former are reversible inhibitors and the later is an irreversible inhibitor of MAO-A. Both in vitro and ex vivo assays were performed on rat brain homogenates, and IC 50 and ID 50 were calculated by a fluorometric method with octopamine as selective MAO-A substrate. In vitro clorgyline and befloxatone were more potent inhibitors than DHP and harmaline with IC 50 values of 1.6 and 7.7 nM vs. 40 and 55 nM; ex vivo ID 50 values were 1.5 and 32 μmol/kg vs. 41 and 49 μmol/kg. Befloxatone had an ID 50/IC 50 ratio four to five times higher than DHP and harmaline. Preincubation time experiments did not distinguish befloxatone from DHP and harmaline. In conclusion, this study shows that DHP behaves as a reversible MAO-A inhibitor whose potency is situated between that of befloxatone and harmaline.