Further studies of the putative serotonin agonist, m-chlorophenylpiperazine: Evidence for a serotonin receptor mediated mechanism of action in humans

Abstract

To further evaluate the effects and mechanism of action of the putative serotonin agonist m-chlorophenylpiperazine (m-CPP) in humans, changes in plasma prolactin, cortisol, growth hormone, ACTH and body temperature were studied in a group of 10 healthy volunteers following oral administration of m-CPP (0.75 mg/kg), before and after pretreatment with the serotonin receptor antagonist metergoline (MTG). M-CPP produced transient significant increases in plasma prolactin, cortisol, ACTH and in body temperature, but did not significantly alter plasma growth hormone concentration. Moreover, pretreatment with the 5HT antagonist metergoline blocked the m-CPP-induced hormonal and temperature changes. These findings provide strong support for m-CPP's effects in humans being mediated through an interaction with 5HT receptors, and thus support the usefulness of m-CPP as a pharmacologic tool for studying disease and drug-induced alterations in serotonin function in man.

Inhibition of monoamine oxidase by moclobemide: effects on monoamine metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers.

“…clomipramine, amitriptyline, imipramine and desipramine, potentiate L-tryptophan-stimulated prolactin release (Charney et al, 1984;Anderson & Cowen, 1986) and, given alone in sufficiently large acute doses, also induce secretion of prolactin (Calil et al, 1984;Laakmann et al, 1985Laakmann et al, , 1986Nutt et al, 1987). Furthermore, fenfluramine, which releases 5-HT and inhibits its neuronal reuptake, stimulates prolactin secretion in man (Quattrone et al, 1983;Lewis & Sherman, 1985), as also does the putative 5-HT receptor agonist m-chlorophenylpiperazine (Mueller et al, 1986). It would be tempting to speculate that the stimulatory effect of moclobemide on prolactin secretion is mediated via serotonergic neurons, but further studies are needed to test this hypothesis.…”

Serotonin1A Receptor Activation by Flesinoxan in Humans Body Temperature and Neuroendocrine Responses

“…cortisol. ACTH (Mueller et al 1986;Charney et al 1987;Kahn et al 1990;Kahn and Wetzler, 1991;KaIus et al 1992), small increases in body temperature, and changes in several mood ratings.…”

“…including euphoria and anxiety in healthy volunteers (Mueller et al 1986). Pretreatment with metergoline and methysergide blocked the changes in levels of PRL and cortisol, as well as the body temperature • changes.…”

Influence of the serotonin antagonist, metergoline, on the anxiogenic effects of carbon dioxide, and on heart rate and neuroendocrine measures, in healthy volunteers

“…We performed a placebo-controlled study of the acute in¯uences of the 5-HT antagonist, metergoline, on the effects of inhalations of air and of CO 2 in healthy volunteers; metergoline had previously been shown to oppose various effects of acute 5-HT agonists and of chronic administration of 5-HT reuptake inhibitors (Benkelfat et al, 1989;Greenberg et al, 1998;Mueller et al, 1986;Pigott et al, 1991Pigott et al, , 1993.…”