Effects of para-methoxyamphetamine and 2,5-dimethoxyamphetamine on serotonergic mechanisms. 
A comparison of serotonergic effects of (+/-)-para-methoxyamphetamine (PMA) and (+/-)-2,5-dimethoxyamphetamine (2,5-DMA) was studied in rats.  The activation of myoclonic twitch activity (MTA) of suprahyoideal muscle in urethane-anesthetized rats has been reported previously to involve central serotonergic and dopaminergic mechanisms.  PMA (0.1--3.2 mg/kg i.v.)  and 2,5-DMA (2--16 mg/kg i.v.)  increased the MTA.  The increased MTA caused by both PMA and 2,5-DMA was blocked by a 5-HT receptor blocker, methysergide, indicating that a serotonergic mechanism was involved.  The increased MTA induced by PMA was reduced by a 5-HT synthesis inhibitor, para-chlorphenylalanine, (pCPA), and by a 5-HT uptake inhibitor, chlorimipramine.  On the other hand, the increased MTA induced by 2,5-DMA was not blocked by pCPA or chlorimipramine.  Using a ventricular perfusion technique in urethane-anesthetized rats, PMA (1.6 mg/kg) effectively increased the release of 3H-radioactivity from brain preloaded with 3H-5-HT before the initiation of perfusion whereas 2,5-DMA (16 mg/kg) decreased the release of 3H-radioactivity.  Analysis of the perfusate by thin layer chromatography for 3H-5-HT and 3H-5-HIAA revealed an increased release of unchanged 3H-5-HT in the perfusate after the injection of PMA.  The ratio of 3H-5-HT to 3H-5-HIAA was markedly increased after PMA but no alteration of this ratio was observed after 2,5-DMA.  It is concluded that PMA elicits its pharmacological action indirectly by releasing 5-HT while 2,5-DMA acts directly on 5-HT receptors.