Neuroendocrine pharmacology of three 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 experimental tools to examine the role of serotonergic nerve terminals in the secretion of hormones. The drugs 1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (MBDB), 5-methoxy-6-methyl-2-aminoindan (MMAI) and p-methylthioamphetamine (MTA) have been suggested to be 5-HT releasers. The present study characterized MBDB, MMAI and MTA by using their effects on the secretion of the hormones adrenal corticotrophin (ACTH), corticosterone, prolactin, oxytocin and renin. The time course of the effect 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 prolactin response did not reach a maximum until 30 min after injection. MBDB increased plasma renin concentration within 10 min, whereas the effect 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, corticosterone, 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 concentrations in a dose-dependent manner. Pretreatment of rats with fluoxetine blocked the ACTH response to MBDB and MMAI, but not to MTA. The prolactin response to all three 5-HT releasers was blocked by fluoxetine. The oxytocin response to MTA and MMAI was inhibited by fluoxetine. The renin responses to all three 5-HT releasers were not significantly inhibited 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.
Li
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Department of Pharmacology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA.
Murakami
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I
Stall
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Levy
A D
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Brownfield
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Nichols
D E
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Van de Kar
L D
LD
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000662:Amphetamines / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D005473:Fluoxetine / Q000494:pharmacology; D007189:Indans / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D010121:Oxytocin / Q000097:blood; D011388:Prolactin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D014667:Vasopressins / Q000097:blood
D015104:3,4-Methylenedioxyamphetamine; D000662:Amphetamines; D005473:Fluoxetine; D007189:Indans; D010121:Oxytocin; D011388:Prolactin; D017367:Selective Serotonin Reuptake Inhibitors; D014667:Vasopressins; C051570:N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine; C068879:5-methoxy-6-methyl-2-aminoindan; C078956:4-methylthioamphetamine