Abstract
Results from animal research suggest that pretreatment with prostaglandin synthesis inhibitors (PGSIs) may inhibit physiological and behavioral effects of moderate ethanol ingestion. We examined the effects of ethanol and pentobarbital in humans with and without pretreatment with indomethacin, a potent PGSI. Ten male subjects with histories of recreational use of ethanol and sedative/hypnotics participated in this inpatient study. The effects of indomethacin alone (0.66 mg/kg), indomethacin (0, 0.17, 0.33, 0.66 and 1.33 mg/kg) in combination with ethanol (0 and 1 g/kg) and indomethacin (0 and 0.66 mg/kg) in combination with pentobarbital (0, 1.33 and 4 mg/kg) were tested. On test days, subjects swallowed capsules containing indomethacin or placebo. One hour later, they swallowed capsules that contained pentobarbital or placebo and a large drink (500 ml) of tonic water that contained ethanol or placebo (tonic water with 2 ml of ethanol floated on top). Both ethanol and pentobarbital affected subjective ratings, performance measures and heart rate. However, indomethacin pretreatment had no influence on drug-induced changes to ethanol and pentobarbital. The results of this study illustrate the relationship between depressant drugs and human performance, but they do not support the hypothesis that inhibition of prostaglandin synthesis diminishes the effects of ethanol and pentobarbital in humans.
Footnotes
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Send reprint requests to: Wallace Pickworth, Ph.D., NIDA, Addiction Research Center, P.O. Box 5180, Baltimore, MD 21224. E-mail:wpickwo{at}irp.nida.nih.gov
- Abbreviations:
- PGSI
- prostaglandin synthesis inhibitor
- PAB
- (Walter Reed) Performance Assessment Battery
- DSST
- digit symbol substitution
- ARCI
- Addiction Research Center Inventory
- BAL
- blood alcohol level
- ANOVA
- analysis of variance
- hsd
- honestly significant difference
- MBG
- morphine-benzedrine group (ARCI subscale)
- PCAG
- pentobarbital-chlorpromazine-alcohol group (ARCI subscale)
- LSD
- lysergic acid diethylamide (ARCI subscale)
- A
- alcohol (ARCI subscale)
- Received March 4, 1997.
- Accepted June 23, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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