Interactions of catecholaminergic receptor blockers with lethal doses of amphetamine or substituted amphetamines in...

Lethality to both isolated and aggregated mice was determined for graded i.p. doses of d-amphetamine, dl-4-methoxyamphetamine (PMA), dl-2,5-dimethoxyamphetamine (DMA), dl-2,5-dimethoxy-4-bromoamphetamine (DOB), dl-2,5-dimethoxy-4-methylamphetamine (DOM) and d1-3,4-methylenedioxyamphetamine (MDA). Haloperidol (2.0 mg/kg), propranolol (10 mg/kg) and phenoxybenzamine (30 mg/kg) were tested for ability to antagonize the lethal effects of amphetamine and its derivatives. Considerable protection against amphetamine lethality was produced by haloperidol in both isolated and aggregated mice and by phenoxybenzamine in isolated mice, but propranolol was ineffective. An equivalent degree of protection was not achieved by use of any of the three agents before PMA, DMA or DOB. Protection against DOM was achieved only with phenoxybenzamine and only for isolated mice. Extensive protection against MDA was supplied by both phenoxybenzamine and propranolol for either condition of housing. Despite close structural relationships between the toxicants, the antidotal effectiveness of the receptor-blocking agents seemed quite limited and specific, and did not support any generalizations.