A pharmacological comparison of 3-methoxy-4,5-methylenedioxyamphetamine and LSD in the dog.

3-Methoxy-4,5-methylenedioxyamphetamine (MMDA), which has been reported to have hallucinogenic actions in man, was compared to LSD in single dose, antagonist interaction, cross-tolerance and appetite suppression studie in the dog. In single doses, MMDA partially resembled LSD: both facilitated the flexor reflex and produced tachypnea, hyperthermia, and analgesia; however, MMDA had greater activity than LSD in producing mydriasis. Only LSD consistently elicited the stepping reflex and produced tachycardia. In both the interaction studies and cross-tolerance studies in LSD-tolerant dogs the effects of MMDA were generally not like those of LSD, except for its spinal cord facilitatory effect. Cyproheptadine antagonized most of the effects of LSD but only the facilitatory effect of MMDA on the flexor reflex. On the other hand, phenoxybenzamine antagonized the mydriasis, analgesia, and hyperthermia caused by MMDA but not LSD. Cross-tolerance to MMDA developed only to its effects on the flexor and skin twitch reflexes. In intact dogs, the anorexigenic potency of MMDA was 16 times less than that of d-amphetamine. It is concluded that MMDA has primarily amphetamine-like activity with some LSD-like actions.