Suppression of pentylenetetrazol-induced seizures by hydralazine associated with 5-hydroxytryptaminergic system in rat brain.

Abstract

The effects of hydralazine on the central nervous system were studied in rats. Administration of hydralazine (10 mg/kg, i.p.) transiently, but significantly suppressed the seizures elicited by pentylenetetrazol (PTZ). The suppressive actions were potentiated in the animals pretreated with either reserpine or p-chlorophenylalanine, but not alpha-methyltyrosine. Methysergide, an antagonist of 5-hydroxytryptamine (5-HT) receptors, could abolish the effect of hydralazine on the tonic component of the seizures, but unlikely that on the clonic one. Although 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels in the brain were both significantly increased after the administration of hydralazine, the increased levels of 5-HIAA reached the peak level earlier than those of 5-HT did. In 5-HT turnover, hydralazine did not change the 5-HT synthesis rate, but the drug inhibited the elimination of 5-HIAA from the brain. The accumulation of 5-HIAA after the inhibition of the acid transport system by probenecid was transiently, but significantly increased in the animals treated with hydralazine. The potency of the suppressive effects of hydralazine on PTZ-induced seizures was in parallel with the rate of 5-HIAA formation in the brain. These results suggest that hydralazine might antagonize the PTZ-induced seizures at least partly by modulating the activation in the central 5-HT-ergic system.