ABSTRACT
The effects of d,1-alpha-methyltyrosine (alphaMT), haloperidol, phenoxybenazmine, propranolol, methysergide and cyproheptadine on the anorexigenic activities of DITA and d-amphetamine were studied in male mice. The pretreatment of mice with methysergide (10 mg/kg, s.c.), cyproheptadine (5 mg/kg, i.p.), phenoxybenzamine (10 mg/kg, i.p.), and propranolol (5 mg/kg, i.p.) failed to alter the anorexigenic effect of DITA and d-amphetamine. On the other hand, alphaMT (32 mg/kg, i.p.) and haloperidol (0.5 mg/kg, i.p.) significantly antagonized the anorexigenic effect of DITA and d-amphetamine. Our data indicate that the anorexigenic activities of DITA and d-amphetamine are mediated mainly through the dopaminergic system.
Subject(s)
Acetophenones/pharmacology , Appetite Depressants/pharmacology , Dextroamphetamine/pharmacology , Dopamine/metabolism , Eating/drug effects , Imidazoles/pharmacology , Acetophenones/antagonists & inhibitors , Animals , Appetite Depressants/antagonists & inhibitors , Cyproheptadine/pharmacology , Dextroamphetamine/antagonists & inhibitors , Haloperidol/pharmacology , Imidazoles/antagonists & inhibitors , Male , Methyltyrosines/pharmacology , Methysergide/pharmacology , Mice , Phenoxybenzamine/pharmacology , Propranolol/pharmacologyABSTRACT
The effect of DL-alpha methyltyrosine (alpha-MT), 6-hydroxydopa (6-OH DOPA), haloperidol, phenoxybenzamine and propranolol on the stimulant activity of the anorexigenic agents (3',4'-dichloro-2-(2-imidazolin-2-yl-thio)-acetophenone HBr) (DITA) and d-amphetamine was studied in male mice. The pretreatment of mice with alpha-MT, (32, 64 mg/kg i.p.), significantly reduced the increase in motor activity induced by DITA or d-amphetamine. On the other hand, pretreatment of mice with 6-OH DOPA, (100, 150 mg/kg, i.v.), did not significantly after the stimulant effect of either DITA or d-amphetamine. In the case of haloperidol, it significantly reduced the increase of motor activity induced by DITA or d-amphetamine; propranolol and phenoxybenzamine were ineffective. Our results support the hypothesis that the stimulant effect of DITA and d-amphetamine depends mainly on the integrity of the central dopaminergic rather than the noradrenergic system.