Simulated car driving as a useful technique for the determination of residual effects and alcohol interaction after short- and long-acting benzodiazepines.
METHODS
54 healthy volunteers took part in 3 placebo controlled double-blind trials designed partly as crossover, partly as parallel group studies. The long-acting (elimination half-life greater than 24 h) test drugs diazepam (DIA 5; 10 mg) and flurazepam (FLU 30 mg) were compared to the short-acting drugs (elimination half-life less than 12 h) lormetazepam (LOR 1.5; 2 mg) and mepindolol sulfate (MEP 10 mg; betablocker) following acute or subchronic application. Alcohol (ALC; 0.4-0.8 per mill blood ALC concentration) was used as a compound interfering with the test drugs. Measurements with the driving simulator TS2 were taken at different times between 1 h and 15 h p.a.


RESULTS
Subchronic use of FLU causes significant impairment of driving performance the next morning in contrast to LOR which even increases the driving ability. The ALC potentiating effect of LOR is larger than that of DIA after acute intake. MEP acts like placebo but reduces blood pressure and heart rate. Interaction of LOR and ALC in the evening does not result in a prolonged hangover effect which could disturb driving performance the next morning.


CONCLUSIONS
Short-acting benzodiazepines without active metabolites have a profound advantage over those with long-acting accumulating characteristics in respect to matutinal car driving ability, if those drugs are used as nighttime hypnotics. These results highlight the necessity of screening hypnotic and tranquilizing drugs concerning their influence on car driving performance at different times after intake and under conditions of interactions with psychotropic drugs, especially alcohol. In view of future methodological requirements a revised model of driving simulation is presented. It is based on a coherent description of the system "driver-vehicle environment" at the level of visual conditions, vehicle behaviour and driver performance. Preliminary data are shown.
D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001334:Automobile Driving; D001569:Benzodiazepines; D003975:Diazepam / Q000494:pharmacology; D004311:Double-Blind Method; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005479:Flurazepam / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008140:Lorazepam / Q000031:analogs & derivatives / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D006993:Hypnotics and Sedatives; C015340:mepindolol; D001569:Benzodiazepines; D000431:Ethanol; D010869:Pindolol; C023842:lormetazepam; D005479:Flurazepam; D008140:Lorazepam; D003975:Diazepam