Neuroendocrine Effects ofM-Chlorophenylpiperazine, a Serotonin Agonist, in Humans

Abstract

M-Chlorophenylpiperazine (m-CPP) produces effects on the central serotonergic system in animals compatiblewith direct agonist activity on postsynaptic serotonin receptors.Although it is a metabolite of the antidepressant trazodone, m-CPP has not previously been given to humans. To evaluate theneuroendocrine, behavioral, and physiological effects of m-CPP,15 normal subjects were given 0.5 mg/kg m–CPP, orally. Administeredacutely under double blind, placebo-controlled conditions,m-CPP was well tolerated by 14 of the 15 subjects; itproduced significant increases in plasma PRL and cortisol andin body temperature, without changing pulse or blood pressure.The mean (SD) maximal increases over baseline for PRL, cortisol and temperature were 13.4 (9.9) ng/ml, 10.1 (6.7) μg/100 ml, and0.4 (0.2) C, respectively. A small but significant increase in selfratedactivation-euphoria and anxiety was noted by some subjects,whereas there were no significant effects on ratings ofdepression, dysphoria, altered self-reality, or functional impairment.These results are similar to those for other serotoninagonists and, thus, suggest that m-CPP merits further study asa pharmacological probe of serotonergic responsivity in humans.The results also support the hypothesis that serotonin plays arole in the regulation of PRL, cortisol, body temperature, andmood.