2-bromoethylamine, a suicide inhibitor of semicarbazide-sensitive amine oxidase, increases hydralazine hypotension in rats.
Previous work has shown that inhibitors of the predominantly vascular enzyme semicarbazide-sensitive amine oxidase (SSAO) potentiate the hypotensive response to hydralazine, itself a SSAO inhibitor, in anesthetized rats. The present study was carried out to determine whether the recently described suicide SSAO inhibitor 2-bromoethylamine shares this effect. Hypotensive responses to hydralazine, 0.1 mg/kg IV, were obtained in chloralose-urethane-anesthetized rats, either unpretreated or receiving bromoethylamine at different doses and pretreatment intervals. Parallel experiments were run with semicarbazide, the prototypical hydrazine SSAO inhibitor. Both inhibitors potentiated hydralazine hypotension, bromoethylamine having a longer latency and a shorter duration of action than semicarbazide. High doses of bromoethylamine did not produce potentiation, a phenomenon attributed to SSAO inactivation by excess substrate and decreased formation by the enzyme of the inhibitor product. Experiments with combined administration of both inhibitors were also carried out. When semicarbazide was administered before bromoethylamine, potentiaton was prevented, apparently by a mechanism similar to the above; when it was given after the amine, potentiation was increased. This was attributed to enzyme inhibition by interaction with 2 different active sites. The charactertistics of hydralazine potentiation by bromoethylamine were considered compatible with the mechanism of SSAO inhibition by the amine.
Vidrio
Horacio
H
Department of Pharmacology, School of Medicine, Universidad Nacional Autonoma de México, México City, México. vidrio@servidor.unam.mx
Medina
Martha
M
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005021:Ethylamines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology*; D007538:Isoniazid / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012663:Semicarbazides / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D005021:Ethylamines; D012663:Semicarbazides; C004504:2-bromoethylamine; D006830:Hydralazine; C010059:carbamylhydrazine; D014700:Verapamil; D006631:Amine Oxidase (Copper-Containing); D007538:Isoniazid