Pharmacologic investigation of compounds related to 3,4-methylenedioxyamphetamine (MDA)

The 3-aminobutane homolog (HMDA) of 3,4-methylenedioxyamphetamine (MDA) was synthesized and compared to MDA for acute pharmacologic/toxicologic properties in mice. The lethality of intraperitoneal doses of HMDA equalled or exceeded that of MDA, depending on whether mice were grouped or isolated after dosing. All deaths with HMDA occurred by 6 hours, while many were delayed to 6-24 hours for MDA, particularly in the aggregated condition. Rather similar response patterns were seen for the N-methylated derivatives of MDA and HMDA. Catecholaminergic receptor blockers, haloperidol, propranolol and phenoxybenzamine, which previously were found protective against MDA lethality, were ineffective against HMDA. However, phenoxybenzamine supplemented a protective action of phenobarbital toward HMDA lethality. The dose-related pattern of locomotor activity effects of HMDA differed from the one seen for MDA, which has been suggested to characterize hallucinogenic agents. Thus, HMDA differs qualitatively in actions from MDA and tends to be more toxic acutely for mice.