Abstract
Brain microdialysis was applied to monitor levels of haloperidol in the rat brain. In anin vitroexperiment, relative recovery through the dialysis membrane was 12-23 % for haloperidol. Using brain microdialysis, we investigated the simultaneous changes of unbound haloperidol and dopamine levels in the extracellular space of the rat striatum after intraperitoneal injection of haloperidol (2 and 5 mg/kg) . After haloperidol injection, the haloperidol concentration in striatal dialysates was increased in a dose-dependent manner, and maximum levels were reached at 90-120 minutes after injection. Thereafter, the haloperidol concentration slowly decreased with a t1/2of approximately 2.5-3 hours. In contrast, the dopamine levels in the striatal dialysates were increased in a dose-dependent manner up to 8 hours after haloperidol injection, peaking at 344 % (2 mg/kg) and 678 % (5 mg/kg) of basal levels. These findings suggest that brain microdialysis is a useful technique for simultaneous alalysis of pharmacokinetics and pharmacodynamics of centrally acting drugs in the brain.
