Effects of MK-801, dantrolene, and FK506 on convulsive seizures and brain nitric oxide production in seizure-susceptible EL mice

Brain Res. 2001 Jan 12;888(2):306-310. doi: 10.1016/s0006-8993(00)03101-2.

Abstract

To clarify the role of nitric oxide (NO) in the pathogenesis of seizures in susceptible EL mice, we investigated effects of three drugs potentially related to NO production, MK-801, dantrolene, and FK506, on convulsive seizures and brain NO metabolites (NOx). MK-801 or dantrolene, but not FK506, suppressed convulsive seizures in EL mice; only MK-801 reduced NOx in the brain. Our results suggested involvement of the N-methyl-D-aspartate receptor-channel complex and intracellular calcium mobilization, but not calcineurin, in the convulsions of EL mice.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiopathology
  • Brain Chemistry / drug effects
  • Calcineurin / metabolism
  • Calcium / metabolism
  • Dantrolene / administration & dosage*
  • Disease Models, Animal
  • Dizocilpine Maleate / administration & dosage*
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Immunosuppressive Agents / administration & dosage
  • Injections, Intraperitoneal
  • Mice
  • Mice, Inbred Strains
  • Muscle Relaxants, Central / administration & dosage
  • Nitrates / analysis
  • Nitrates / metabolism
  • Nitric Oxide / biosynthesis*
  • Nitrites / analysis
  • Nitrites / metabolism
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Seizures / drug therapy*
  • Seizures / metabolism
  • Seizures / physiopathology
  • Tacrolimus / administration & dosage*

Substances

  • Excitatory Amino Acid Antagonists
  • Immunosuppressive Agents
  • Muscle Relaxants, Central
  • Nitrates
  • Nitrites
  • Receptors, N-Methyl-D-Aspartate
  • Nitric Oxide
  • Dizocilpine Maleate
  • Calcineurin
  • Dantrolene
  • Calcium
  • Tacrolimus