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.