Stable anticonvulsant action of benzodiazepines during development in rats

J Pharm Pharmacol. 1993 Sep;45(9):807-10. doi: 10.1111/j.2042-7158.1993.tb05690.x.

Abstract

The anticonvulsant action of midazolam and clonazepam was studied in 168 immature rats in three age groups (12, 18 and 25 days old). Epileptic after-discharges of the spike-and-wave type accompanied by clonic seizures of facial and forelimb muscles induced by stimulation of sensorimotor cortex were used as a model. The solvent used for clonazepam exhibited a tendency to anticonvulsant action in 12-day-old rats. On the contrary, a proconvulsant action was seen in 25-day-old animals. The action of both benzodiazepines was identical and did not change substantially during development. The highest dose used (1 mg kg-1, i.p.) shortened the duration of epileptic after-discharges, the two lower doses (0.1 and 0.02 mg kg-1, i.p.) suppressed the progressive prolongation with repeated stimulations seen under control conditions. Motor correlates of stimulation remained practically uninfluenced by the two benzodiazepines, myoclonic seizures accompanying epileptic after-discharges were attenuated by the highest dose of both drugs.

MeSH terms

  • Aging*
  • Animals
  • Animals, Newborn
  • Anticonvulsants / pharmacology*
  • Anticonvulsants / therapeutic use
  • Clonazepam / pharmacology*
  • Clonazepam / therapeutic use
  • Electric Stimulation
  • Electroencephalography / drug effects
  • Epilepsy / drug therapy*
  • Midazolam / pharmacology*
  • Midazolam / therapeutic use
  • Rats
  • Rats, Wistar
  • Seizures / drug therapy*

Substances

  • Anticonvulsants
  • Clonazepam
  • Midazolam