Nalmefene causes greater hypothalamic-pituitary-adrenal axis activation than naloxone in normal volunteers: implications for the treatment of alcoholism.
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.
Schluger
J H
JH
The Laboratory of the Biology of the Addictive Diseases, The Rockefeller University, New York, New York 10021-6399, USA.
Ho
A
A
Borg
L
L
Porter
M
M
Maniar
S
S
Gunduz
M
M
Perret
G
G
King
A
A
Kreek
M J
MJ
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
D009292:Narcotic Antagonists; D009270:Naloxone; D009271:Naltrexone; D000324:Adrenocorticotropic Hormone; C038981:nalmefene; D006854:Hydrocortisone