No abstract

While outpatients or other users of therapeutic drugs have to be informed about the risk of impaired functioning during driving or work, the prescribing physician needs to be familiar with the side effects of alternative drugs in order to select the most suitable treatment. With this aim, several types of benzodiazepine anxiolytics in low anxiolytic doses (diazepam 5 mg or 10 mg, nitrazepam 5 mg, oxazepam 10 mg, medazepam 10 mg, and alprazolam 0.2 or 0.5 mg-per 2m2 body surface) were tested under laboratory conditions for their effects on vigilance performance. In a double-blind design, 145 healthy volunteers performed a 60 min vigilance test (composed of discriminatory reactions to acoustic stimuli and a secondary visual tracking task) and four short psychomotor tests (lasting 1-7 min each) before and after a single dose of drug or placebo. Subjects described their perception of the drug effect with the help of a mood check list, and fatigue, sleepiness, and effort scales. Only diazepam 5 mg and 10 mg, alprazolam 0.5 mg, and nitrazepam 5 mg caused significant deterioration in vigilance performance along with perceived sleepiness and the need for a greater effort to overcome it. The onset of diazepam effect was quicker, whereas alprazolam effect lasted longer. No effect was noted in the short psychomotor tests except for the Bourdon Cancellation Test, where the first phase of diazepam effect was registered.

No abstract

No abstract

Benzene (B), toluene (T), ethylbenzene (EB), styrene (S) and xylene isomers (oX, mX, pX) are important environmental pollutants and B is a proved human carcinogen. Their inhalation by male Wistar rats (4 mg/l, 20 h/day, 4 days) caused cytochrome P450 (P450) induction. The degree of P450 2B1 induction increased and that of 2E1 decreased in the series B, T, EB, S, oX, mX and pX, as estimated by Western blots, while neither solvent was as effective for 2B1 induction as phenobarbital and B was more effective for 2E1 than ethanol. The levels of several other P450s decreased after exposure to these solvents, B being most effective. Exposure to these solvents increased in vitro hepatic microsomal oxidation of B and aniline (AN) (2E1 substrates) 3 to 6-fold, indicating induction of this P450. T oxidation was increased 2 to 4-fold and chlorobenzene (ClB) oxidation 3-fold. Sodium phenobarbital (PB, 80 mg/kg/day, 4 days, i.p.) did not increase ethylmorphine (EM) and benzphetamine (BZP) demethylation (2B1 substrates), neither of the B derivatives did so, and oX decreased it; however, pentoxyresorufin O-dealkylation was well related to the immunochemically detected 2B1 levels in control, PB and B microsomes. PB did not increase B, but increased T and ClB oxidation 2-4 and 3-fold, respectively, indicating possible 2B1 role in their oxidation. B oxidation after various inducers was related to immunochemical 2E1 levels, T and ClB oxidation to both 2B1 and 2E1 and AN oxidation to 2E1 and 1A2 levels.(ABSTRACT TRUNCATED AT 250 WORDS)