Hydroxytryptamine uptake inhibitors block para- methoxyamphetamine-induced 5-HT release.

1 Activation of mycolonic twitch activity (MTA) of suprahyoideal muscle after p-methoxyamphetamine (PMA) administration in rats anaesthetized with urethane has previously been reported to be due to brain 5-hydroxytryptamine (5-HT) release. Increased MTA caused by PMA was blocked by chlorimipramine (0.1 to 1 mg/kg) and fluoxetine (0.3 to 3 mg/kg) but not by desipramine (3 mg/kg). 2 The 5-hydroxytryptophan-induced increase of MTA of suprahyoideal muscle in rats pretreated with pargyline was not blocked by chlorimipramine but was blocked by methysergide. 3 [3H]-5-HT was injected intraventricularly 30 min before the beginning of ventricular perfusion with artificial cerebrospinal fluid in urethane anaesthetized rats. PMA (mg/kg i.v.) increased the release of [3H]-5-HT in the perfusate after injection. Chlorimipramine (0.1 to 1 mg/kg) and fluoxetine (0.1 to 1 mg/kg), injected 10 min before the PMA injection, caused a dose-related blockade of the increased release of [3H]-5-HT induced by PMA. Desipramine at 3 mg/kg slightly inhibited the increased release of [3H]-5-HT caused by PMA but was inactive at 1 mg/kg. 4 It is proposed that these 5-HT uptake inhibitors block the increased MTA caused by PMA by preventing the PMA-induced release of 5-HT in the central nervous system.