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 IC50 and ID50 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 IC50 values of 1.6 and 7.7 nM vs. 40 and 55 nM; ex vivo ID50 values were 1.5 and 32 micromol/kg vs. 41 and 49 micromol/kg. Befloxatone had an ID50/IC50 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.
Gerardy
Jean
J
Department of Pharmacology, Institute of Pathology, Belgium.
Dresse
Albert
A
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002227:Carbazoles / Q000494:pharmacology*; D003010:Clorgyline / Q000494:pharmacology; D006246:Harmaline / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008995:Monoamine Oxidase / Q000187:drug effects / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D002227:Carbazoles; D008996:Monoamine Oxidase Inhibitors; D010080:Oxazoles; C090014:befloxatone; C067315:3,3a-dehydropyrazidol; D006246:Harmaline; D008995:Monoamine Oxidase; D003010:Clorgyline