Behavioral and biochemical effects of para-methoxyphenylethylamine

p-methoxyphenlethylamine (p-MPEA) induces the "serotonin syndrome" in mice which consists of lateral head weaving, Straub tail, hindlimb abduction, tremor, hyperactivity, reciprocal fore-paw treading, salivation and piloerection. These p-MPEA-induced behavioral signs were partially prevented by pretreatment with serotonin (5HT) uptake blockers (fluoxetine, chlorimipramine, Org 6582) and 5HT receptor blockers (methiothepin, methysergide, cinnanserin) but not by two depletors of brain 5HT (p-chlorophenylalanine, reserpine). p-MPEA selectively released 5HT and inhibited 5HT uptake from mouse whole brain synaptosomes. The concentrations of both 5HT and 5-hydroxyindoleacetic acid (5HIAA) in whole mouse brain were increased at 1 and 2 hours after injection of p-MPEA (50 mg/kg). The effect of p-MPEA on displacement of specific tritiated 5HT binding to membranes from mouse brain was considerably less than that of p-chlorophenylethylamine (p-CPEA), p-methoxytryptamine (pMT) and quipazine. Thus p-MPEA may induce the "serotonin syndrome" predominantly by releasing 5HT from presynaptic nerve terminals.