engleski

The assesment of anticonvulsant properties of the drug – pentylenetetrazole seizure model

The need for new antiepileptic drugs and the appropriate model for their identification are always present. Different approaches can be used and one of them also used in our laboratory is systemic administration of the chemoconvulsant pentylenetetrazol (PTZ), a non-competitive GABA antagonist. Namely, minimal doses of PTZ needed to induce different stages of seizure are recorded as a seizure threshold. During experiments the threshold for different types of seizures (myoclonic twitch, generalized clonus with loss of righting reflexes, and tonic backward extension of forelimbs, and death) are assessed using i.v. application of PTZ, while the traditional seizure test with PTZ s.c. injection accounts for generalized clonic seizures in mice. The most important factors which influence an estimation of the drug anticonvulsive potency in PTZ seizure model are bishaped dose-response curve (decline in anticonvulsant dose-response at high doses), the route of PTZ administration (i.v. vs. s.c.), species and strain differences in drug metabolism, differences in drug potencies (administered doses compared to ‘active’ drug concentrations in plasma), endpoints used for PTZ test, etc. Namely, i.v. PTZ seizure threshold may be useful in assessing the anticonvulsant effect of the drug at different stages of convulsions although the important role of technical, biological and pharmacologicalfactors in the interpretation of the results should be taken into account. In conclusion, PTZ seizure model is effective in predicting the efficacy of a substance against the myoclonic petit mal seizures in humans, though one can not predict the drug efficacy against absence seizures.

epilepsy; anticonvulsant drugs; pentylenetetrazol; experimental seizures

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