This work was supported in part by the National Institutes of Health-National Institute on Drug Abuse Research Center Grant DA-P50-05130, National Institutes of Health-National Institute on Drug Abuse Research Scientific Award Grant K05-DA00049, and the National Institutes of Health-National Center for Research Resources (NCRR) General Clinical Research Center Grant M01-RR00102.
Nalmefene Causes Greater Hypothalamic-Pituitary-Adrenal Axis Activation than Naloxone in Normal Volunteers: Implications for the Treatment of Alcoholism
Article first published online: 30 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 22, Issue 7, pages 1430–1436, October 1998
How to Cite
Schluger, J. H., Ho, A., Borg, L., Porter, M., Maniar, S., Gunduz, M., Perret, G., King, A. and Kreek, M. J. (1998), Nalmefene Causes Greater Hypothalamic-Pituitary-Adrenal Axis Activation than Naloxone in Normal Volunteers: Implications for the Treatment of Alcoholism. Alcoholism: Clinical and Experimental Research, 22: 1430–1436. doi: 10.1111/j.1530-0277.1998.tb03931.x
- Issue published online: 30 MAY 2006
- Article first published online: 30 MAY 2006
- Received for publication January 7, 1998; accepted May 13, 1998
- Opioid Antagonist;
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 μ-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 preceptor, and has a higher affinity for K- and §-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 K- and 8-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.