Actions and interactions of hypnotics on human performance: single doses of zopiclone, triazolam and alcohol.
Actions and interactions with ethanol (0.8 g/kg) of triazolam (TRZ, 0.25 mg) and zopiclone (ZOP, 7.5 mg) on performance and memory were studied with 12 healthy young subjects. The randomized double-blind and crossover test sessions were carried out at 1-week intervals. Each time a set of performance tests and self-assessments on visual analogue scales were done before the treatment and 1.5, 3, 4.5, 6 and 8 h after it. The clinical test for drunkenness (CTD) was done 2 and 5 h after drug intake. Venous blood was sampled after each set of tests. Both TRZ and ZOP impaired coordinative and reactive skills, but not peripheral attention or body balance. They also impaired cognitive test performance (digit substitution, symbol copying), and lowered flicker fusion threshold. The psychomotor effects of the two hypnotics and measures of subjective sedation peaked at 1.5 and 3 h. Spatial memory was impaired by TRZ at 4.5 h. Cognitive tests and tracking were most sensitive to alcohol. Furthermore alcohol impaired both motor and vestibular aspects of the CTD while both ZOP and TRZ alone had only minor effects. Alcohol enhanced and prolonged the effects of both hypnotics without modifying their plasma concentrations. Drug-alcohol interactions were mainly additive though more obvious with TRZ. Interactions were evident also on the CTD. The hypnotics were free from residual psychomotor and cognitive effects at 8 h even after the coadministration of alcohol. It is concluded that ZOP and TRZ have a mainly additive interaction with alcohol but pharmacokinetic mechanisms do not seem to contribute essentially to this.
Department of Pharmacology, University of Helsinki, Finland.
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T
Kuitunen
M J
MJ
Mattila
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T
Seppala
D000328:Adult; D000428:Alcohol Drinking / Q000523:psychology*; D000435:Alcoholic Intoxication / Q000523:psychology; D001143:Arousal / Q000187:drug effects; D001288:Attention / Q000187:drug effects; D053961:Azabicyclo Compounds; D004311:Double-Blind Method; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D016032:Randomized Controlled Trials as Topic; D011930:Reaction Time / Q000187:drug effects; D014229:Triazolam / Q000494:pharmacology*
D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; C515050:zopiclone; D014229:Triazolam; D000431:Ethanol