PHARMACOLOGICAL EVIDENCE FOR CENTRAL SEROTONERGIC EFFECTS OF MONOMETHOXYAMPHETAMINES

Abstract

The effects of 3 monomethoxyamphetamines, dl-p-methoxyamphetamine (dl-PMA), dl-m-methoxyamphetamine (dl-MMA) and dl-o-methoxyamphetamine (dl-OMA) and d-amphetamine (d-A) on the myoclonic twitch activity (MTA) of suprahyoideal muscle in rats and locomotor activity in rats and mice were studied. PMA, MMA and d-A increased the MTA, but OMA was ineffective. The increased MTA induced by d-A was not influenced by the blockade of 5-hydroxytryptamine (5-HT) receptor by methysergide or inhibition of 5-HT synthesis by p-chlorophenylalanine (PCPA) but was reduced by haloperidol which blocked the dopamine receptor. The increased MTA produced by PMA was not influenced by haloperidol but was reduced by methysergide and PCPA. The increased MTA induced by MMA was not effectively blocked by either PCPA or haloperidol but was blocked by the combination of both PCPA and haloperidol. Whereas the increased MTA produced by d-A is probably not dependent on the availability of 5-HT, PMA probably exerts its effect by a release of 5-HT, and the MMA effect may be due to a release of both 5-HT and dopamine. High doses of PMA and MMA increased locomotor activity and produced hyperthermia, but OMA was inactive. The findings agree with previous biochemical findings that PMA releases 5-HT in brain tissue and suggest that PMA exerts its pharmacological effects by releasing 5-HT.