Skip to main content
Log in

Effects ofm-chlorophenylpiperazine in normal subjects: a dose-response study

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

m-Chlorophenylpiperazine (MCPP), a direct 5HT receptor agonist, was administered orally to 20 normal subjects in two doses (0.25 and 0.5 mg/kg) in a placebo-controlled design. Behavioral responses; ACTH, cortisol, prolactin and MCPP blood level; temperature and pulse rate were measured over a 210-min period after administration of tablets. Non-linear dose-response relationships between MCPP and ACTH, cortisol and prolactin response were found. On the higher dose, a significant increase in the number of physical symptoms was also noted and three subjects (15%) had a panic attack, while one subject (5%) had a panic attack on the lower dose. No effects on other behavioral variables, pulse rate and temperature were found using either dose. These findings attest to the usefulness of MCPP as a challenge agent to assess 5HT receptor hypersensitivity when given at a low oral dose (i.e. around 0.25 mg/kg), and to assess 5HT receptor hyposensitivity when given at higher oral doses (i.e. around 0.5 mg/kg).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aloi JA, Insel TR, Mueller EA, Murphy DL (1984) Neuroendocrine and behavioral effects of MCPP in Rhesus monkeys. Life Sci 34:1325–1331

    Google Scholar 

  • Aulakh CS, Cohen RM, Hill JL, Murphy DL, Zohar J (1987) Long-term imipramine treatment enhances locomotor and food intake suppressant effects ofm-chlorophenylpiperazine in rats. Br J Pharmacol 91:747–752

    Google Scholar 

  • Aulakh CS, Wozniak KM, Haas M, Hill JL, Zohar J, Murphy DL (1988) Food intake, neuroendocrine and temperature effects of 8-OHDPAT in the rat. Eur J Pharmacol 146:253–259

    Google Scholar 

  • Caccia S, Ballabio M, Samanin R, Zanini MG, Garattini S (1981) MCPP, a central 5HT agonist, is a metabolite of Trazodone. J Pharm Pharmacol 33:477–478

    Google Scholar 

  • Charney DS, Woods SW, Goodman WK, Heninger GR (1987) Serotonin function in anxiety. II. Effects of the serotonin agonist MCPP in panic disorder patients and healthy subjects. Psychopharmacology 92:14–24

    Google Scholar 

  • Charney DS, Goodman WK, Price LH, Woods SW, Rasmussen SA, Heninger GR (1988) Serotonin function in obsessive-compulsive disorder: a comparison of the effects of tryptophan andm-chlorophenylpiperazine in patients and healthy subjects. Arch Gen Psychiatry 45:177–185

    Google Scholar 

  • Chrousos G, Schulte HM, Oldfield EH, Gold PhW, Cutler GB, Loriaix DL (1984) The corticotropin-releasing factor stimulation test. N Engl J Med 310:622–626

    Google Scholar 

  • Conn PJ, Sanders-Bush E (1987) Relative efficacies of piperazines at the phosphoinositide hydrolysis-linked serotonergic (5HT2 and 5HT1c) receptors. J Pharmacol Exp Ther 242:552–557

    Google Scholar 

  • Cunningham KA, Appel JB (1986) Possible 5-hydroxytryptaminel receptor involvement in the stimulus properties of 1-(m-trifluoromethylphenyl) piperazine. J Pharmacol Exp Ther 237:369–377

    Google Scholar 

  • Endicott F, Spitzer RL (1978) A diagnostic interview: the schedule for affective disorders and schizophrenia. Arch Gen Psychiatry 35:837–844

    Google Scholar 

  • Fuller RW, Snoddy HD, Mason NR, Owen JE (1981) Disposition and pharmacological effects of MCPP. Neuropharmacology 20:155–162

    Google Scholar 

  • Hamik A, Peroutka SJ (1989) 1-(m-Chlorophenyl)piperazine (mCPP) interactions with neurotransmitter receptors in the human brain. Biol Psychiatry 25:569–575

    Google Scholar 

  • Heninger GR, Krystal JH, Smith A (1988) Effects of D1 and D2 receptor antagonists and 5HT receptor agonists and antagonists on neuroendocrine function in rhesus monkeys. Abstr Soc Neurosci 324:7

    Google Scholar 

  • Hoyer D (1988) Functional correlates of serotonin 5HT1 recognition sites. J Recept Res 8:59–81

    Google Scholar 

  • Hoyer D, Pazos A, Probst A, Palacios JM (1986) Serotonin receptors in the human brain. I. Characterization and autoradiographic localization of 5-HT1A recognition sites. Apparent absence of 5-HT1B recognition sites. Brain Res 376:85–96

    Google Scholar 

  • Invernizzi R, Cotecchia S, DeBlaise A (1981) Effects of MCPP on receptor binding and brain metabolism of monoamines in rats. Neurochem Int 3:239–244

    Google Scholar 

  • Kahn RS, Asnis GM, Wetzler S, van Praag HM (1988) Neuroendocrine evidence for serotonin receptor supersensitivity in patients with panic disorder. Psychopharmacology 96:360–364

    Google Scholar 

  • Kennet GA, Curzon G (1988) Evidence that hypophagia induced by mCPP and TFMPP requires 5HT1c and 5HT1b receptors; hypophagia induced by RU 24969 requires only 5HT1b receptors. Psychopharmacology 96:93–100

    Google Scholar 

  • Kilpatrick GJ, Jones BJ, Tyers MB (1987) Identification and distribution of 5HT3 receptors in rat brain using radioligand binding. Nature 330:746–748

    Google Scholar 

  • McNair DM, Lorr M, Droppelman LF (1971) Manual for the Profile of Mood States, Educational and Industrial testing Service, San Diego, California

  • Mueller EA, Sunderland T, Murphy DL (1985) Neuroendocrine effects ofm-CPP, a serotonin agonist, in humans. J Clin Endocrinol Metab 61:1179–1184

    Google Scholar 

  • Mueller EA, Murphy DL, Sunderland T (1986) Further studies of the putative serotonin agonist,m-chlorophenylpiperazine evidence for a serotonin receptor mediated mechanism of action in humans. Psychopharmacology 89:388–391

    Google Scholar 

  • Munaro NI (1978) The effects of ovarian steroids on hypothalamic 5-hydroxytryptamine neuronal activity. Neuroendocrinology 26:270–276

    Google Scholar 

  • Pettibone DJ, Williams M (1984) Serotonin-releasing effects of substituted piperazines in vitro. Biochem Pharmacol 33:1531–1535

    Google Scholar 

  • Quattrone, G Schettini G, Annunziato L, DiRenzo G (1981) Pharmacological evidence of supersensitivity of central serotonergic receptors involved in the control of prolactin secretion. Eur J Pharmacol 76:9–13

    Google Scholar 

  • Samanin R, Mennini T, Ferraris A, Bendotti C, Borsini F (1980) Hyper and hyposensitivity of central serotonin receptor: [3H]serotonin binding and functional studies in the rat. Brain Res 189:449–457

    Google Scholar 

  • Smith TM, Suckow RF (1985) Trazodone andm-chlorophenylpiperazine. Concentration in brain and receptor activity in regions in the brain associated with anxiety. Neuropharmacology 24:1067–1071

    Google Scholar 

  • Spitzer RL, Endicott J, Robins E (1978) Research Diagnostic Criteria: rationale and reliability. Arch Gen Psychiatry 35:773–782

    Google Scholar 

  • Zohar J, Mueller EA, Insel TR, Zohar-Kadouch RC, Murphy DL (1987) Serotonergic responsivity in obsessive compulsive disorder: comparison of patients and healthy controls. Arch Gen Psychiatry 44:946–951

    Google Scholar 

  • Zohar J, Insel TR, Zohar-Kadouch RC, Hill JL, Murphy DL (1988) Serotonergic responsivity in obsessive compulsive disorder: effects of chronic clomipramine treatment. Arch Gen Psychiatry 45:167–172

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kahn, R.S., Wetzler, S., Asnis, G.M. et al. Effects ofm-chlorophenylpiperazine in normal subjects: a dose-response study. Psychopharmacology 100, 339–344 (1990). https://doi.org/10.1007/BF02244603

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02244603

Key words

Navigation