Hormonal and temperature responses to flesinoxan in normal volunteers: an antagonist study.
BACKGROUND
Flesinoxan is a highly potent and selective 5-HT1A agonist. In a recent study, in normal volunteers, flesinoxan induced a significant and dose-dependent increase in adrenocorticotropic hormone (ACTH), cortisol, prolactin (PRL), growth hormone (GH) and a decrease in body temperature.


OBJECTIVE
In order to better define the role of 5-HT receptor subtypes in response to flesinoxan, we assessed the influence of 5-HT1A and 5-HT2 antagonists on hormonal and temperature responses to flesinoxan.


METHODS
Hormonal and temperature responses were studied in 6 volunteers with or without pretreatment with pindolol (30 mg p.o.), a 5-HT1A antagonist, or ritanserin (10 mg p.o.), a selective 5-HT2 antagonist, using a double-blind crossover design.


RESULTS
Pindolol significantly antagonized ACTH, PRL, GH and temperature responses to flesinoxan and ritanserin exhibited similar activity on PRL and ACTH responses.


CONCLUSIONS
These results show the role of 5-HT1A mechanisms in the PRL, ACTH, GH, and temperature responses to flesinoxan, and the role of 5-HT2 mechanisms in PRL and ACTH responses. Therefore, they confirm the interest of flesinoxan as a 5-HT neuroendocrine probe.
Pitchot
William
W
Psychiatric Unit, CHU Sart Tilman, B-4000 Liège, Belgium. wpitchot@chu.ulg.ac.be
Wauthy
Jacques
J
Legros
Jean-Jacques
JJ
Ansseau
Marc
M
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004341:Drug Evaluation; D004347:Drug Interactions; D013006:Growth Hormone / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006728:Hormones / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D010869:Pindolol / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood; D011863:Radioimmunoassay / Q000379:methods; D011985:Receptors, Serotonin / Q000502:physiology*; D016713:Ritanserin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013997:Time Factors
D006728:Hormones; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D016713:Ritanserin; C056895:flesinoxan; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013006:Growth Hormone; D010869:Pindolol; D006854:Hydrocortisone