Flunitrazepam (1 and 2 mg), diazepam (10 and 20 mg) or placebo was adm
inistered to healthy, male volunteers, and the time course of psychomo
tor impairment, as indicated by simple and complex choice reaction tim
e and movement time, was studied during a period of 6 h after drug int
ake. To examine whether acute tolerance developed, the observed perfor
mance during decreasing drug plasma concentration was compared to the
predicted performance based on kinetic-dynamic modelling of the observ
ed performance during the first 1.5 h after intake when the drug plasm
a concentrations were increasing or at peak level. Placebo corrections
of the test scores were accomplished to adjust for diurnal variation
and the possible influence of learning during the test day. After the
flunitrazepam treatments, the predictions overestimated the actual per
formance significantly with respect to simple and choice reaction time
at the 6-h session after intake. After the diazepam treatments, howev
er, no significant deviation was detected between predicted and observ
ed performance. The results indicate that acute tolerance develops wit
h respect to impairment of attention demanding performance after mediu
m to large doses of flunitrazepam, and that tolerance is expressed aft
er approximately 4-6 h following intake.