NALMEFENE CAUSES GREATER HYPOTHALAMIC-PITUITARY-ADRENAL AXIS ACTIVATION THAN NALOXONE IN NORMAL VOLUNTEERS - IMPLICATIONS FOR THE TREATMENTOF ALCOHOLISM

Among other actions, opioid antagonists modulate the control endogenou s opioids exert on the hypothalamic-pituitary-adrenal (HPA) axis. Nalo xone, nalmefene, and naltrexone are the opioid antagonists approved fo r use in man and are primarily mu-opioid selective. Naltrexone and nal mefene have been demonstrated to be useful in the treatment of alcohol ism. Compared with naloxone, nalmefene has a longer half-life, is more potent at the Ct-receptor, and has a higher affinity for kappa- and d elta-opioid receptors. We conducted an inpatient study comparing the e ffects of 10 and 30 mg doses of intravenous naloxone and nalmefene in normal, nonsubstance nor alcohol-abusing, volunteers. Significant incr eases in ACTH and cortisol were observed after both antagonists, witho ut an apparent dose-response relationship; however, both doses of nalm efene resulted in greater HPA axis activation than either dose of nalo xone (ACTH: p <0.005). These results indicate that kappa- and delta-op ioids may play important roles in the regulation of the HPA axis; nalm efene may be useful as both a probe to explore the HPA axis physiology and as a pharmacotherapeutic agent.