Electroencephalographic study on sedative effect of talipexole, a novel antiparkinsonian drug, in rats with chronic electrode implants

Talipexole (B-HT 920 CL₂) is expected to be a novel antiparkinsonian drug with higher efficacy and lesser gastrointestinal side effects as compared with conventional dopamine receptor agonists. On the other hand, because of D₂ and α₂-autoreceptor stimulation by talipexole, it produces more marked sedative effects in clinical trial and animal behavioral studies. In the present experiments, electroencephalographic (EEG) effects of talipexole were investigated in unanesthetized rats with chronic electrode implants. The changes in the spontaneous EEG were evaluated during dark time with rats which had been housed in a room maintained on a reversed light dark cycle (lights on from 19 : 00 to 7 : 00) for 7 days. Talipexole at 10 μg/kg, s.c. induced a slight drowsy pattern: high voltage slow waves in the frontal cortex and disappearance of hippocampal theta rhythm. At doses of 32 and 100 μg/kg, s.c., talipexole caused a more marked drowsy pattern in the spontaneous EEG and significant decreases in the sedative score assessed by simultaneous observations of the EEG and behavioral motor activities. On the other hand, bromocriptine at 1 and 10 mg/kg, s.c. caused only a slight and temporal drowsy pattern in the spontaneous EEG without changing the arousal score. Then, the EEG arousal response induced by electrical stimulation of the mesencephalic reticular formation was studied during light time in rats which had been housed in a room maintained on a normal light dark cycle (lights on from 7 : 00 to 19 : 00). Both talipexole and bromocriptine slightly increased the threshold voltage to induce arousal response; however, the drug induced changes were not dose dependent. These results indicate that talipexole exhibits a sedative effect at much lower doses than bromocriptine, and that its sedative effect seems to he relatively weak and quite different from those noted with sleep inducers