Tizanidine protects mice against convulsions induced by lidocaine: involvement of alpha 2-adrenoceptors.

The effects of alpha-adrenoceptors agents on seizures induced by intraperitoneal administration of lidocaine (75 mg/kg) were studied in mice. Pretreatment with the selective alpha 2-adrenoceptor agonist, tizanidine, decreased the incidence of seizures induced by lidocaine. Tizanidine increased the latency to the first seizure in those animals which progressed to seizures. The blockade of alpha 2-adrenoceptors with yohimbine or phentolamine counteracted the protection induced by tizanidine. The selective alpha 2-adrenoceptor antagonist, prazosin, did not modify the protection induced by tizanidine. The alpha 2-adrenoceptor agonist clonidine also increased the latency to the first seizure induced by lidocaine. The protective effect of clonidine was also reversed by pretreatment with the selective alpha 2-adrenoceptor antagonist yohimbine. Taken together, these results suggest that alpha 2-adrenoceptors are involved in seizures induced by lidocaine.