ANALYSIS OF THE MECHANISM OF ANTICONVULSANT ACTION OF 3,4-DICHLOROPHENYL PROPENYL ISOBUTYLAMIDE (7903)

The mechanism of anticonvulsant action of 7903 was studied. It may be related to serotoninergic system. 7903 was found to be able to increase the concentration of 5-HT and 5-HIAA in mice brain. The peak time of such action was at the first hour after treatment and gradually returned to normal level within 12 hours. This change of 5-HT was closely related to its anticonvulsant action, the correlation coefficent was 0.93 (P<0.001). Results of other experiments further support this finding. Reserpine was shown to antagonize the anticonvulsant action of 7903. Reserpinized mice were pretreated with L-tryptophane, the precursor of 5-HT, to supplement the concentration of depleted 5-HT (nearly to 80%).In such a condition, the anticonvulsant action of 7903 was recovered. In contrast, normal mice pretreated with PCPA to block the synthesis of 5-HT, decreased the anticonvulsant action of 7903.The concentration of NE was slightly decreased at the first hour after treatment with 7903, then gradually increased, and reached a peak on the 12th hours after treatment. At this time, the anticonvulsant action of the drug completely disappeared. The concentration of DA did not change within the 12-hour period.