The Study Of Effects Of Tiapride On Kindled Models

Tiapride is a substitude benzamide with selective dopamine D₂ and D3-antagonist properties which appears to have preferential affinity for extra-striatal dopamine receptors. However, the antiepileptic effect of tiapride on animal chronic kindling model has not been reported.Objective: To investigate the antiepileptic effect of tiapride on amygdale kindling models in rats and combine tiapride with phenotoin or valproate or nicardipine to observe the effect on their antiepileptic actions. Furthermore, we observe the effect of tiapride on spontaneous activity of mice .Methods: To produce the amygdale kindling model and observe the effects and mechanism of tiapride on the kindling seizure activity ,the effects of tiapride on general antiepileptic drugs are also observed by combination-administration. The effect of the different dose tiapride on spontaneous activity of mice were observed by photo—cell method. And in the MES experiment, we observe the effect of tiapride on the rates of seizure.Results: Tiapride, at dose of 80 mg.kg^-1 ip, can inhibit the seizure of kindled rats, raise the focal afterdischarge threshold; all at ineffective doses on kindling model, the combination of tiapride(50 mg.kg^-1) with nicardipine shows no significant effect on ADD and Racine's stages(P > 0.05); but it has synergic effects with phenotoin or valproate; tiapride can inhibit the spontaneous activity of the mice, but can not inhibit the rate of seizure in mice.Conclusion: The results suggest that tiapride can inhibit seizure activity of amygdale kindling models and has synergism with phenotoin or valproate at ineffective doses on kindling; the mechanism probably is related to enhancing the function of GABA system and inhibiting Na⁺ channel. And we also conclude that tiapride can product center sedation.