Effect of various antiepileptic drugs in a pentylenetetrazol-induced seizure model in mice.

The present study was undertaken to compare the anticonvulsant effect of various antiepileptic drugs on the intravenous pentylenetetrazol (PTZ)-induced seizure threshold in mice. Minimal doses of PTZ needed to induce different phases (myoclonic jerks, generalized clonus and tonic extensor) of convulsions were recorded as an index of seizure threshold. Furthermore, TID50 (the dose of an anticonvulsant drug required to increase the PTZ seizure threshold for tonic extensor by 50%) was calculated for all drugs, and from these values the potency ratio was determined. Pentobarbital (10-40 mg/kg i.p.), phenobarbital (5-20 mg/kg i.p.), phenytoin (20-40 mg/kg i.p.), carbamazepine (5-20 mg/kg i.p.), diazepam (0.5-2 mg/kg i.p.), chlordiazepoxide (1-4 mg/kg i.p.), triazolam (0.02-0.08 mg/kg i.p.), clonazepam (0.03125-0.25 mg/kg i.p.), GABA (25-100 mg/kg i.p.), ethanol (1000-4000 mg/kg of 10% v/v p.o.), ashwagandha (50-200 mg/kg p.o.), tiagabine (20 and 40 mg/kg i.p.), gabapentin (50-200 mg/kg i.p.), pregabalin (10-40 mg/kg i.p.), progesterone (20-80 mg/kg s.c.), adenosine (25-200 mg/kg i.p.) and rofecoxib (1-4 mg/kg i.p.) exhibited dose-dependent anticonvulsant effects. The TID50 of triazolam was found to be the lowest among all the drugs tested, indicating higher potency. The relative potency of standard drugs to increase the PTZ seizure threshold for tonic extensor was found to be: triazolam > clonazepam > diazepam > rofecoxib > chlordiazepoxide > phenobarbital > carbamazepine > pentobarbital > pregabalin > phenytoin > progesterone > tiagabine > GABA > adenosine > gabapentin > ashwagandha > ethanol. The results of the present study indicate that the intravenous PTZ seizure threshold may be useful for assessing the anticonvulsant effect of drugs effective against different stages of convulsions.

Rofecoxib potentiates the anticonvulsant effect of topiramate.

The present study examines the effect of rofecoxib in combination with topiramate (a newer antiepileptic) against PTZ (80 mg/kg, i. p.)-induced chemoconvulsions in mice. Pretreatment with rofecoxib (1.0 and 5.0 mg/kg., i. p.) or topiramate (50 and 100 mg/kg., i. p.) dose dependently protected the animals against PTZ-induced convulsions. However, the lower dose of neither rofecoxib (0.5 mg/kg., i. p.) nor topiramate (25 mg/kg., i. p.) modified the latency of any of the phase of PTZ-induced convulsions. When a subeffective doses of rofecoxib (0.5 mg/kg, i. p.) was coadministered with a subprotective dose of topiramate (25 mg/kg, i. p.), there was no increase in onset latency of myoclonic jerks but an increase in the latency for clonus and extensor phase were observed. Rofecoxib may be used as an adjunct therapy with topiramate in the treatment of epilepsy.