Effects of alcohol, zolpidem, and some other sedatives and hypnotics on human performance and memory.
Zolpidem (Zol), an omega1-agonist, acts via GABA(A) receptors but may differ qualitatively from diazepam (Dz) and other benzodiazepines (BZDs). We conducted a placebo-controlled, randomized, double-blind, and crossover study to compare the psychomotor and cognitive effects of 15 mg Zol with those of 15 mg Dz, 30 mg oxazepam (Ox), 7.5 mg zopiclone (Zop), and ethanol (EOH; 0.65 + 0.35 g x kg(-1)) given to 12 subjects at 1-week intervals. Psychomotor tests (symbol digit substitution, simulated driving, flicker fusion, body sway) were done before and 1, 3.5, and 5 h after intake; immediate and delayed memory were measured between 1.5 and 3.5 h. The plasma concentrations of drugs were measured by gas chromatography and by radioreceptor assay (RRA). The mean values of EOH in blood at 1.5, 4, and 5.5 h were 0.82, 0.88, and 0.6 g x l(-1), and the mean values of RRA-assayed plasma Dz were 470, 330, and 210 microg x l(-1), respectively. The corresponding values of other hypnosedatives, in Dz equivalents (microg x l(-1)), were 550, 750, and 330 for Ox; 350, 270, and 70 for Zol; and 160, 210, and 70 for Zop. The standard RRA graph for Zol was significantly flatter than those for other hypnotics. Zol impaired coordinative, reactive, and cognitive skills at 1 and 3.5 h more clearly than the other agents did, the most sensitive performance (tracking) still being impaired by Zol at 5 h. Dz and Zop were less active than Zol objectively; subjective sedation after Dz and Zol was stronger than after Zop. Compared to placebo, all active agents tended to impair learning and memory, their decremental effects, in declining order, being Zol, Dz > EOH, Ox > Zop. During the delay, Dz and Zol caused similar losses of material that had been learned. When separating "true" delayed memory from immediate memory (attention important), Dz and Zol had equieffects on delayed memory and were more detrimental than Zop. When contrasting that against the impaired psychomotor performances, it is possible that 15 mg Zol impairs memory relatively less than 15 mg Dz does.
Mattila
M J
MJ
Institute of Biomedicine (Department of Pharmacology and Toxicology), University of Helsinki, Finland.
Vanakoski
J
J
Kalska
H
H
Seppälä
T
T
D000328:Adult; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects*; D011725:Pyridines / Q000097:blood / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D000077334:Zolpidem
D002492:Central Nervous System Depressants; D006993:Hypnotics and Sedatives; D011725:Pyridines; D000431:Ethanol; D000077334:Zolpidem