Circadian variations of lorazepam-induced neurologic deficits

Circadian variations of lorazepam-induced neurologic deficits were tested in mice. The duration of the impairment after administration of 3 mg/kg lorazepam was considerably shorter at 2100 h compared to other times of the day. No significant variations could be found for brain concentrations of drug at recovery and 15 or 30 min after drug administration. Food intake did not seem to account for the circadian pattern observed. It was therefore concluded that chronergy of lorazepam is a result of altered sensitivity of the animal over time rather than to altered pharmacokinetics.