Pharmacological evidence for the central serotonergic effects of monomethoxyamphetamines

The effects of three monomethoxyamphetamines, dl para methoxyamphetamine (dl PMA), dl meta methoxyamphetamine (dl MMA) and dl ortho 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 were found to increase 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 para chlorophenylalanine (PCPA) but was reduced by haloperidol which blocked the dopamine receptor. On the other hand, 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. The results indicate that whereas the increased MTA produced by d A is not dependent on the availabiliy of 5 HT, PMA exerts its effect by a release of 5 HT and that the MMA effect is due to a release of both 5 HT and dopamine. High doses of PMA and MMA increased the locomotor activity and produced hyperthermia but OMA was inactive. The findings are in agreement with previous biochemical findings that PMA releases 5 HT in brain tissue and suggests that PMA exerts its pharmacological effects by releasing 5 HT.