5-HYDROXYTRYPTAMINE UPTAKE INHIBITORS BLOCK PARA-METHOXYAMPHETAMINE-INDUCED 5-HT RELEASE

Activation of myoclonic 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). 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. [3H]‐5‐HT was injected intraventricularly 30 min before the beginning of ventricular perfusion with artificial cerebrospinal fluid in urethane anaesthetized rats. PMA (2 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. 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. 1979 British Pharmacological Society