EFFECTS OF ALCOHOL, ZOLPIDEM, AND SOME OTHER SEDATIVES AND HYPNOTICS ON HUMAN-PERFORMANCE AND MEMORY

Zolpidem (Zol), an omega(1)-agonist, acts via GABA(A) receptors but ma y differ qualitatively from diazepam (Dz) and other benzodiazepines (B ZDs). We conducted a placebo-controlled, randomized, double-blind, and crossover study to compare the psychomotor and cognitive effects of 1 5 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 . kg(-1)) given to 12 subjects at 1-week intervals. Psychomotor tests (symbol digit substitution, si mulated driving, nicker fusion, body sway) were done before and 1, 3.5 , and 5 h after intake; immediate and delayed memory were measured bet ween 1.5 and 3.5 h. The plasma concentrations of drugs were measured b y 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 . l(- 1), and the mean values of RRA-assayed plasma Dz were 470, 330, and 21 0 mu g . l(-1), respectively. The corresponding values of other hypnos edatives, in Dz equivalents (mu g . l(-1)), were 550, 750, and 330 for Ox; 350, 270, and 70 for Zol; and 160, 210, and 70 for Zop. The stand ard RRA graph for Zol was significantly flatter than those for other h ypnotics. Zol impaired coordinative, reactive, and cognitive skills at 1 and 3.5 h more clearly than the other agents did, the most sensitiv e performance (tracking) still being impaired by Zol at 5 h. Dz and Zo p were less active than Zol objectively; subjective sedation after Dz and Zol was stronger than after Zop. Compared to placebo, ail active a gents 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. Wh en separating ''true'' delayed memory from immediate memory (attention important), Dz and Zol had equieffects on delayed memory and were mor e detrimental than Zop. When contrasting that against the impaired psy chomotor performances,it is possible that 15 mg Zor impairs memory rel atively less than 15 mg Dz does. (C) 1998 Elsevier Science Inc.