Abstract α-Sanshool is an alkamide isolated from the stem bark of Zanthoxylum liebmannianum, a Mexican medicinal plant known as Colopahtle. Our research group has reported that the intraperitoneal administration of α-sanshool induces tonic-clonic seizures in mice. In the present study, we investigated the convulsive effect of this alkamide and elucidated its mechanism of action by comparing with well-known convulsive and anticonvulsive drugs in an in vivo approach. α-Sanshool showed a potent (ED50 [CL 95%]=3.06 [2.92–3.22] mg/kg) and immediate (2±2 s) seizure effect after the intraperitoneal administration in mice. The convulsive effect of this alkamide was only observed for intraperitoneal administration; the oral route did not show any effect. α-Sanshool was less potent than strychnine (ED50 [CL 95%]=1.53 [1.44–1.62] mg/kg), but more effective than bicuculline, 4-aminopyridine, affinin, and pentylenetetrazol, in that order. The seizures induced by α-sanshool were reduced by capsazepine and diazoxide, suggesting the involvement of TRPV1 and potassium channels in the mechanism of action of this compound.