NEUROENDOCRINE PHARMACOLOGY OF 3 SEROTONIN RELEASERS - 1-(1,3-BENZODIOXOL-5-YL)-2-(METHYLAMINO)BUTANE (MBDB), 5-METHOXY-6-METHYL-2-AMINOINDAN (MMAI) AND P-METHYLTHIOAMPHETAMINE (MTA)

Serotonin (5-hydroxytryptamine, 5-HT)-releasing drugs are important ex perimental tools to examine the role of serotonergic nerve terminals i n the secretion of hormones. The drugs 1-(1,3-benzodioxol-5-yl)-2-(met hylamino)butane (MBDB), 5-methoxy-6-methyl-2-aminoindan (MMAI) and p-m ethylthioamphetamine (MTA) have been suggested to be 5-HT releasers. T he present study characterized MBDB, MMAI and MTA by using their effec ts on the secretion of the hormones adrenal corticotrophin (ACTH), cor ticosterone, prolactin, oxytocin and renin. The time course of the eff ect of MBDB, MMAI and MTA (5 mg/kg, i.p.) showed that the peak effect on plasma ACTH occurred 10 min after the injection, whereas the prolac tin response did not reach a maximum until 30 min after injection. MBD B increased plasma renin concentration within 10 min, whereas the effe ct of MTA was significant only at 30 min after injection. All three 5- HT releasers decreased HR (within 5 min) and blood pressure (at 15 min after injection). MBDB, MMAI and MTA increased plasma ACTH, corticost erone, prolactin and renin levels in a dose-dependent manner, whereas no changes were observed in plasma vasopressin concentrations. MTA and MMAI, but not MBDB, significantly increased plasma oxytocin concentra tions in a dose-dependent manner. Pretreatment of rats with fluoxetine blocked the ACTH response to MBDB and MMAI, but not to MTA. The prola ctin response to all three 5-HT releasers was blocked by fluoxetine. T he oxytocin response to MTA and MMAI was inhibited by fluoxetine. The renin responses to all three 5-HT releasers were not significantly inh ibited by fluoxetine. The results suggest that MBDB, MMAI and MTA can increase the secretion of several hormones, at least in part, through stimulation of serotonergic neurotransmission. However, these three 5- HT releasers seem to have effects on other (and as yet uncharacterized ) mechanisms that can stimulate the secretion of some hormones.