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POTENTIATION OF FENFLURAMINE‐INDUCED ACTH RELEASE IN MAN BY NALOXONE
Author(s) -
Jackson Richard V.,
Grice Jeffrey E.,
Jackson A. Jane,
Vella Rodney D.
Publication year - 1989
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1989.tb01555.x
Subject(s) - fenfluramine , endocrinology , medicine , basal (medicine) , (+) naloxone , hydrocortisone , adrenocorticotropic hormone , chemistry , serotonin , opioid , hormone , receptor , insulin
SUMMARY 1. This study set out to compare the effect of the combination of fenfluramine (Fen) and naloxone (Nal) on ACTH and cortisol release with each of these agents alone in six normal volunteers. Three protocols were used: 1.5 mg/kg bodyweight oral Fen; 125 μg/kg bodyweight i.v. Nal; oral Fen plus i.v. Nal 135 min later. Plasma ACTH and cortisol were measured at intervals of 285 min over each test. 2. The mean peak levels and mean peak changes from basal in plasma ACTH and cortisol were significantly greater in the combination test (Fen/Nal) than in either the Fen alone or the Nal alone tests. Fen and Nal given together cause a synergistic release of ACTH and cortisol as determined by the areas under the ACTH‐time and cortisol‐time curves for Fen/Nal compared to the sums of Fen alone plus Nal alone curves for ACTH and cortisol. 3. We conclude that Fen and Nal acting synergistically work through different and potentiating mechanisms at the hypothalamic, central nervous system and/or pituitary levels to cause ACTH release.