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

Methods Find Exp Clin Pharmacol. 2009 Sep;31(7):423-32. doi: 10.1358/mf.2009.31.7.1393610.

Abstract

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.

MeSH terms

  • Adenosine / pharmacology
  • Algorithms
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anticonvulsants / therapeutic use*
  • Barbiturates / therapeutic use
  • Carbamazepine / therapeutic use
  • Central Nervous System Depressants / pharmacology
  • Convulsants*
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Epilepsy, Tonic-Clonic / chemically induced
  • Epilepsy, Tonic-Clonic / drug therapy
  • Ethanol / pharmacology
  • Infusions, Intravenous
  • Lactones / pharmacology
  • Male
  • Mice
  • Pentylenetetrazole*
  • Phenytoin / therapeutic use
  • Plant Extracts
  • Seizures / chemically induced*
  • Seizures / drug therapy*
  • Sulfones / pharmacology
  • Withania / chemistry

Substances

  • Anti-Inflammatory Agents
  • Anticonvulsants
  • Barbiturates
  • Central Nervous System Depressants
  • Convulsants
  • Cyclooxygenase 2 Inhibitors
  • Lactones
  • Plant Extracts
  • Sulfones
  • rofecoxib
  • Carbamazepine
  • Ethanol
  • Phenytoin
  • Adenosine
  • Ashwagandha
  • Pentylenetetrazole