Further Studies of the Putative Serotonin Agonist, M-chlorophenylpiperazine: Evidence for a Serotonin Receptor Mediated Mechanism of Action in Humans

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 1986 Jan 1

PMID 3014595

Citations 18

Authors

E A Mueller

D L Murphy

T Sunderland

Affiliations

Soon will be listed here.

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.

Citing Articles

The Role of Metabolites of Antidepressants in the Treatment of Depression.

Rudorfer M, Potter W CNS Drugs. 2016; 7(4):273-312.

PMID: 27520753 DOI: 10.2165/00023210-199707040-00003.

Updated overview of the putative role of the serotoninergic system in obsessive-compulsive disorder.

Aouizerate B, Guehl D, Cuny E, Rougier A, Burbaud P, Tignol J Neuropsychiatr Dis Treat. 2008; 1(3):231-43.

PMID: 18568072 PMC: 2416754.

Daily administration of m-chlorophenylpiperazine to healthy human volunteers rapidly attenuates many of its behavioral, hormonal, cardiovascular and temperature effects.

Benjamin J, Greenberg B, Murphy D Psychopharmacology (Berl). 1996; 127(2):140-9.

PMID: 8888380 DOI: 10.1007/BF02805987.

Eating disorder and obsessive-compulsive disorder: neurochemical and phenomenological commonalities.

Jarry J, Vaccarino F J Psychiatry Neurosci. 1996; 21(1):36-48.

PMID: 8580116 PMC: 1188732.

Effect of pindolol on the L-5-HTP-induced increase in plasma prolactin and cortisol concentrations in man.

Meltzer H, Maes M Psychopharmacology (Berl). 1994; 114(4):635-43.

PMID: 7855226 DOI: 10.1007/BF02244995.

References

Mueller E, Murphy D, Sunderland T . Neuroendocrine effects of M-chlorophenylpiperazine, a serotonin agonist, in humans. J Clin Endocrinol Metab. 1985; 61(6):1179-84. DOI: 10.1210/jcem-61-6-1179. View

Ferrari C, Reschini E, Peracchi M, Crosignani P . Endocrine profile and therapeutic employment of a new prolactin-lowering drug, metergoline. Gynecol Obstet Invest. 1980; 11(1):1-16. DOI: 10.1159/000299801. View

Quattrone A, Tedeschi G, Aguglia U, Scopacasa F, Direnzo G, Annunziato L . Prolactin secretion in man: a useful tool to evaluate the activity of drugs on central 5-hydroxytryptaminergic neurones. Studies with fenfluramine. Br J Clin Pharmacol. 1983; 16(5):471-5. PMC: 1428066. DOI: 10.1111/j.1365-2125.1983.tb02202.x. View

Meltzer H, Robertson A, TRICOU B, Lowy M . Enhanced serum cortisol response to 5-hydroxytryptophan in depression and mania. Life Sci. 1983; 33(25):2541-9. DOI: 10.1016/0024-3205(83)90164-9. View

Chrousos G, Schulte H, Oldfield E, Gold P, Cutler Jr G, Loriaux D . The corticotropin-releasing factor stimulation test. An aid in the evaluation of patients with Cushing's syndrome. N Engl J Med. 1984; 310(10):622-6. DOI: 10.1056/NEJM198403083101004. View

Willner P . Antidepressants and serotonergic neurotransmission: an integrative review. Psychopharmacology (Berl). 1985; 85(4):387-404. DOI: 10.1007/BF00429653. View

Checkley S . Neuroendocrine tests of monoamine function in man: a review of basic theory and its application to the study of depressive illness. Psychol Med. 1980; 10(1):35-53. DOI: 10.1017/s0033291700039593. View

Aloi J, Insel T, Mueller E, Murphy D . Neuroendocrine and behavioral effects of m-chlorophenylpiperazine administration in rhesus monkeys. Life Sci. 1984; 34(14):1325-31. DOI: 10.1016/0024-3205(84)90003-1. View

Samanin R, Mennini T, Ferraris A, Bendotti C, Borsini F, Garattini S . Chlorophenylpiperazine: a central serotonin agonist causing powerful anorexia in rats. Naunyn Schmiedebergs Arch Pharmacol. 1979; 308(2):159-63. DOI: 10.1007/BF00499059. View

10.

Leysen J, Awouters F, Kennis L, Laduron P, Vandenberk J, Janssen P . Receptor binding profile of R 41 468, a novel antagonist at 5-HT2 receptors. Life Sci. 1981; 28(9):1015-22. DOI: 10.1016/0024-3205(81)90747-5. View

11.

Fuller R, Snoddy H, Mason N, Owen J . Disposition and pharmacological effects of m-Chlorophenylpiperazine in rats. Neuropharmacology. 1981; 20(2):155-62. DOI: 10.1016/0028-3908(81)90198-2. View

12.

Siever L, Murphy D, Slater S, de la Vega E, Lipper S . Plasma prolactin changes following fenfluramine in depressed patients compared to controls: an evaluation of central serotonergic responsivity in depression. Life Sci. 1984; 34(11):1029-39. DOI: 10.1016/0024-3205(84)90016-x. View

13.

Caccia S, Fong M, Garattini S, Zanini M . Plasma concentrations of trazodone and 1-(3-chlorophenyl)piperazine in man after a single oral dose of trazodone. J Pharm Pharmacol. 1982; 34(9):605-6. DOI: 10.1111/j.2042-7158.1982.tb04807.x. View

14.

Cavagnini F, Raggi U, Micossi P, Di Landro A, Invitti C . Effect of an antiserotoninergic drug, metergoline, on the ACTH and cortisol response to insulin hypoglycemia and lysine-vasopressin in man. J Clin Endocrinol Metab. 1976; 43(2):306-12. DOI: 10.1210/jcem-43-2-306. View

15.

Lamberts S, MacLeod R . Metergoline and other peripheral serotonin antagonists inhibit prolactin secretion through mechanisms unrelated to serotonin. Proc Soc Exp Biol Med. 1979; 162(1):75-9. DOI: 10.3181/00379727-162-40621. View

16.

Casanueva F, Villanueva L, Penalva A, Cabezas-Cerrato J . Depending on the stimulus, central serotoninergic activation by fenfluramine blocks or does not alter growth hormone secretion in man. Neuroendocrinology. 1984; 38(4):302-8. DOI: 10.1159/000123908. View

17.

Fuller R . Serotonergic stimulation of pituitary-adrenocortical function in rats. Neuroendocrinology. 1981; 32(2):118-27. DOI: 10.1159/000123142. View

18.

Fuller R, Mason N, Molloy B . Structural relationships in the inhibition of [(3)H]serotonin binding to rat brain membranes in vitro by 1-phenyl-piperazines. Biochem Pharmacol. 2010; 29(5):833-5. DOI: 10.1016/0006-2952(80)90567-5. View

19.

Quattrone A, Schettini G, Annunziato L, Renzo G . Pharmacological evidence of supersensitivity of central serotonergic receptors involved in the control of prolactin secretion. Eur J Pharmacol. 1981; 76(1):9-13. DOI: 10.1016/0014-2999(81)90003-0. View

20.

Imura H, Nakai Y, Yoshimi T . Effect of 5-hydroxytryptophan (5-HTP) on growth hormone and ACTH release in man. J Clin Endocrinol Metab. 1973; 36(1):204-6. DOI: 10.1210/jcem-36-1-204. View