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.
Alcoholism: Clinical & Experimental Research – Wiley
Published: Oct 1, 1998
Keywords: ; ; ; ;
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