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

Abstract

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 microM) were significantly greater than nonflushers (1.4 +/- 0.5 microM) following ethanol ingestion (p less than 0.001). Ethanol alone always induced a significant rise in facial skin temperature [mean area under the curve (AUC) = 5142 +/- 648 % delta T x min, p less than 0.01] and of pulse (mean AUC = 1622 +/- 120 bpm x min, p less than 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-induced rise in facial skin temperature of flushers by 58 +/- 14% (p less than 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.

The Role of Acetaldehyde in the Actions of Alcohol (Update 2000)

“…These initial findings were confirmed by subsequent studies in which the prostaglandin synthesis inhibitor indomethacin attenuated the chlorpropamide alcohol flushing in white subjects (Barnett et al, 1980(Barnett et al, , 1981a. In line with these results is the Asian finding that alcohol flushing is blocked by both aspirin (Truitt et al, 1987) and indomethacin (Ho et al, 1988). In addition to the flushing results, more recently it has been demonstrated that AcH-induced bronchoconstriction in Japanese asthmatic patients can be blocked by prostaglandin synthesis inhibitors (Fujimura et al, 1997;Myou et al, 1994).…”

“…On the other hand, the peptide release was not associated with flushing in another study (Johnston et al, 1984). The antagonism of the opiate receptors by nalmefene has been found to inhibit alcohol flushing in Asians (Ho et al, 1988). Naloxone has been found to inhibit chlorpropamide alcohol flushing (Leslie et al, 1979) and alcohol flushing related to rosacea (Bernstein and Soltani, 1982).…”

Lifestyle, stress and cortisol response: Review II

“…Approximately 50% of certain Asian groups are ALDH 2 deficient [40][41][42] . ALDH 2 deficiency is very uncommon among other non-Mongolian ethnic groups [40][41][42] . These studies demonstrated higher levels of cortisol following an alcohol challenge in Asians who experience alcohol-induced flushing.…”

“…It is also well established that long-term alcohol consumption induces endocrine abnormalities, especially in the HPA axis 26) . Three independent studies of investigators examined cortisol levels in Asian subjects who either did or did not show alcoholinduced flushing [40][41][42] . Approximately 50% of certain Asian groups are ALDH 2 deficient [40][41][42] .…”

“…Three independent studies of investigators examined cortisol levels in Asian subjects who either did or did not show alcoholinduced flushing [40][41][42] . Approximately 50% of certain Asian groups are ALDH 2 deficient [40][41][42] . ALDH 2 deficiency is very uncommon among other non-Mongolian ethnic groups [40][41][42] .…”