Tolerance to the anticonvulsant effect of clorazepate and clonazepam in mice

Pharmacol Toxicol. 1988 Jan;62(1):38-41. doi: 10.1111/j.1600-0773.1988.tb01841.x.


The rate of development of tolerance to the benzodiazepines clorazepate and clonazepam against pentetrazole-induced seizures in mice was compared. Treatment with clorazepate (0.1% solution as drinking water) for 21 days led to tolerance beginning at day 7. When mice were treated with clonazepam (0.5 mg/kg twice daily intraperitoneally), tolerance was evident already at the fourth day of treatment. Twenty-four hours after cessation of treatment the seizure threshold was significantly decreased after treatment with both drugs. Clorazepate, a prodrug of the main metabolite of diazepam, desmethyldiazepam, regards further interest for anticonvulsant therapy because of a relatively slow onset of tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Benzodiazepines
  • Clonazepam / pharmacology*
  • Clorazepate Dipotassium / pharmacology*
  • Drug Tolerance
  • Male
  • Mice
  • Pentylenetetrazole
  • Seizures / chemically induced
  • Seizures / drug therapy*
  • Time Factors


  • Anti-Anxiety Agents
  • Benzodiazepines
  • Clonazepam
  • Clorazepate Dipotassium
  • Pentylenetetrazole