Antagonism of reserpine rigidity without inducing sedation.

The effects of pretreatment with chlorpromazine, promethazine or SKF 7265 on the severity of reserpine-induced rigidity were evaluated using a series of behavioral responses. Chlorpromazine (10 mg/kg) reduced the severity of the syndrome, particularly the tremor, but only at doses that also produced marked sedation. SKF 7265 was more effective than chlorpromazine and produced no detectable sedation or other motor impairment. Promethazine was ineffective in protecting against the effects of reserpine. These studies demonstrate that motor and behavioral abnormalities induced by high doses of reserpine can be blocked without inducing generalized sedation. This would suggest that it is possible to separate pharmacologically the motor pathways responsible for reserpine rigidity and those responsible for sedation.