Cumulative effects of penfluridol, a long-acting neuroleptic drug, as assayed by its behavioral actions

Penfluridol, a long-acting neuroleptic drug, was repeatedly given to rats well trained on the discriminated avoidance schedule (intertrial interval, 25 sec; warning duration, 5 sec), and accumulation of the effects were investigated by observing the behavioral changes. When penfluridol was orally given in a dose of 2-8 mg/kg once daily for 10 consecutive days, the suppression of avoidance response was progressively enhanced until the 3rd-4th day. But from the 4th day, the maximum level of suppression was maintained during the later medication. On its withdrawal, the avoidance response was gradually restored, returning to the initial level in 3-4 days. When 8 mg/kg was given at 1-2 weeks after the withdrawal, the same suppression was observed as after the single administration of the same dose. The progressive enhancement of suppression in the early half of the medication period evidently indicated the cumulative effect. The degree of suppression during the plateau showed a linear correlation with the dosage, and was estimated to be about 3,5 times as high as in the corresponding single administration.