Opiate Antagonist Nalmefene Inhibits Ethanol‐induced Flushing in Asians: A Preliminary Study

Ethanol‐induced flushing (EIF) occurs in up to 80% of Asians and is characterized by facial flushing, tachycardia, and increased cardiac output. Since endogenous opiates and prostaglandins may be mediators of flushing syndromes, we attempted to block EIF in four Asian flushers with single doses of either the opiate antagonist nalmefene, or the prostaglandin synthesis inhibitor indomethacin. Nonflushers (2 Caucasian, 2 Asian) and four Asian flushers were given on separate days water, ethanol (0.4 g/kg p.o.), ethanol plus nalmefene (2 mg i.v.), or ethanol plus indomethacin (50 mg p.o.). Ethanol concentrations of flushers and nonflushers were similar. Mean (±SEM) plasma acetaldehyde concentrations of flushers (28.2 ± 11.8 μM) were significantly greater than nonflushers (1.4 ± 0.5 μM) following ethanol ingestion (p < 0.001). Ethanol alone always induced a significant rise in facial skin temperature [mean area under the curve (AUC) = 5142 ± 648 %ΔT± min, p < 0.01] and of pulse (mean AUC = 1622 ± 120 bpm ± min, p < 0.001) in flushers compared to water ingestion. A single dose of nalmefene (2 mg i.v.) but not indomethacin (50 mg p.o.), reduced the mean (±SEM) ethanol‐in‐duced rise in facial skin temperature of flushers by 58 ± 14% (p < 0.05) without changing plasma acetaldehyde concentrations. These data are preliminary evidence that the opiate antagonist, nalmefene, blocks some of the vascular manifestations of EIF without altering the elevated plasma concentrations of acetaldehyde.