The behavioural effects of lorazepam are poorly related to its concentration in the brain.
The brain and plasma pharmacokinetics of lorazepam were investigated in rats that had received 5 once daily injections of 0.5 or 1.0 mg/kg of the compound. The sedative effects of the drug were also assessed using a holeboard test. Thirty minutes after the final injection of 1.0 mg/kg lorazepam animals showed a similar degree of sedation to animals tested 90 min after their final injection of 0.5 mg/kg, despite having brain concentrations of lorazepam that were 3 times higher. Four hours after 0.5 mg/kg lorazepam, when the concentration of lorazepam in the brain was very low, animals' head-dipping and locomotor activity scores were still only 60% of the controls' scores. It is concluded that brain concentrations of lorazepam are of little use in predicting the behavioural effects of the compound.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism*; D007700:Kinetics; D008140:Lorazepam / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats
D014151:Anti-Anxiety Agents; D008140:Lorazepam