Reversal of the acute effects of 3,4-methylenedioxymethamphetamine by 5-HT uptake inhibitors.

Recent evidence suggests that the acute 3,4-methylenedioxymethamphetamine (MDMA)-induced loss of tryptophan hydroxylase activity (TPH) may be due to the oxidation of critical sulf-hydryl groups on the molecule. To determine if TPH activity could be regenerated in vivo we administered a 5-HT uptake inhibitor at various times immediately after MDMA. Although enzyme activity began to decline immediately following MDMA administration, rats receiving the uptake inhibitor 1 h post MDMA showed a rapid recovery of TPH activity. Administration of an uptake inhibitor 3 h post MDMA was without effect on the time course of TPH inactivation. The results suggest that systems exist within the serotonergic neuron for the reductive regeneration of active TPH. Furthermore, these systems are acutely compromised following the administration of MDMA.