Reference

Fenfluramine, p-chloroamphetamine and p-fluoroamphetamine stimulation of pituitary-adrenocortical activity in rat: evidence for differences in site and mechanism of action

Fenfluramine, p-chloroamphetamine and p-fluoroamphetamine stimulation of pituitary-adrenocortical activity in rat: evidence for differences in site and mechanism of action. McElroy, J. F.; Miller, J. M.; Meyer, J. S. (Dep. Psychol., Univ. Massachusetts, Amherst, MA, USA). J. Pharmacol. Exp. Ther., 228(3), 593-9 (English) 1984. CODEN: JPETAB. ISSN: 0022-3565. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Serum corticosterone [50-22-6] concns. were measured in rats after injection of fenfluramine (FEN) [458-24-2], p-chloroamphetamine (PCA) [64-12-0], and p-fluoroamphetamine (PFA) [459-02-9], halogenated amphetamine derivs. believed to exert their behavioral and physiol. effects through the release and/or depletion of brain serotonin (5-HT) [50-67-9]. Systemic administration of FEN, PA or PFA caused a dose-dependent corticosterone elevation, with a potency rank ordering of PCA > FEN > PFA. Chronic depletion of brain 5-HT by pretreatment with p-chlorophenylalanine or 5,7-dihydroxytryptamine antagonized the PCA-induced elevation, but not that produced by FEN or PFA. When injected intracerebroventricularly, PCA and PFA elevated corticosterone levels whereas FEN did not. The central PCA-induced elevation was prevented by pretreatment with either the 5-HT reuptake inhibitor fluoxetine or the 5-HT receptor blocker methysergide. Fluoxetine or methylsergide also antagonized the corticosterone elevation produced by systemically injected PCA or FEN, but not that produced by PFA. Pretreatment with dexamethasone, an inhibitor of pituitary ACTH secretion, prevented the corticosterone elevation produced by all 3 drugs. 459-02-9 and 50-22-6 which are cas registry numbers of substances are two of reagents here. Thus, despite their structural and pharmacol. similarities, FEN, PCA and PFA each act differently to stimulate corticosterone secretion. As expected, PCA elevates corticosterone levels through a central serotonergic mechanism that requires the continued synthesis and storage of 5-HT. The effect of FEN is also serotonergically mediated but appears to be either peripheral in origin or mediated via stimulation of postsynaptic 5-HT receptors. Finally, although the precise mode of action of PFA on the pituitary-adrenocortical system remains unclear, 5-HT is apparently not involved in such action. .