Differential behavioural and neurochemical effects of para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine in the rat.

1. This study was prompted by recent deaths that have occurred after recreational administration of the substituted amphetamine para-methoxyamphetamine (PMA). Because relatively little is known regarding its mechanism(s) of action, its effects on physiological, behavioural and neurochemical parameters were compared with the well known effects of 3,4-methylenedioxymethamphetamine (MDMA). 2. Equivalent doses of PMA (5-20 mg/kg) produced greater hypothermia than MDMA at an ambient temperature of 20 degrees C. At 30 degrees C, PMA continued to evoke hypothermia except the highest dose where hyperthermia ensued. MDMA altered body temperature only at the highest dose where hyperthermia also resulted. 3. At both 20 and 30 degrees C, MDMA stimulated locomotor activity whereas PMA had modest effects and then, only at high doses. 4. In vivo chronoamperometry was used to measure the effect of MDMA and PMA on release, and inhibition of uptake, of serotonin (5-HT) and dopamine (DA) in the dorsal striatum of anaesthetised rats. As expected, MDMA evoked release of DA and inhibited uptake of both DA and 5-HT. By contrast, PMA was a relatively weak releasing agent and did not inhibit DA uptake. However, PMA potently inhibited uptake of 5-HT. 5. Taken together these data suggest that the acute adverse effects of PMA are more likely to be associated with alterations in serotonergic rather than dopaminergic neurotransmission.