title: Nalmefene causes greater hypothalamic-pituitary-adrenal axis activation than naloxone in normal volunteers: implications for the treatment of alcoholism.
abstract: Among other actions, opioid antagonists modulate the control endogenous opioids exert on the hypothalamic-pituitary-adrenal (HPA) axis. Naloxone, nalmefene, and naltrexone are the opioid antagonists approved for use in man and are primarily mu-opioid selective. Naltrexone and nalmefene have been demonstrated to be useful in the treatment of alcoholism. Compared with naloxone, nalmefene has a longer half-life, is more potent at the mu-receptor, and has a higher affinity for kappa- and delta-opioid receptors. We conducted an inpatient study comparing the effects of 10 and 30 mg doses of intravenous naloxone and nalmefene in normal, nonsubstance nor alcohol-abusing, volunteers. Significant increases in ACTH and cortisol were observed after both antagonists, without an apparent dose-response relationship; however, both doses of nalmefene resulted in greater HPA axis activation than either dose of naloxone (ACTH: p <0.005). These results indicate that kappa- and delta-opioids may play important roles in the regulation of the HPA axis; nalmefene may be useful as both a probe to explore the HPA axis physiology and as a pharmacotherapeutic agent.
authors.affiliation: The Laboratory of the Biology of the Addictive Diseases, The Rockefeller University, New York, New York 10021-6399, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Schluger
authors.forename: A
authors.initials: A
authors.lastname: Ho
authors.forename: L
authors.initials: L
authors.lastname: Borg
authors.forename: M
authors.initials: M
authors.lastname: Porter
authors.forename: S
authors.initials: S
authors.lastname: Maniar
authors.forename: M
authors.initials: M
authors.lastname: Gunduz
authors.forename: G
authors.initials: G
authors.lastname: Perret
authors.forename: A
authors.initials: A
authors.lastname: King
authors.forename: M J
authors.initials: MJ
authors.lastname: Kreek
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000097:blood / Q000534:rehabilitation*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000627:therapeutic use*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D009292:Narcotic Antagonists; D009270:Naloxone; D009271:Naltrexone; D000324:Adrenocorticotropic Hormone; C038981:nalmefene; D006854:Hydrocortisone