Effects of Lamotrigine on brain nitrite and cGMP levels during focal cerebral ischemia in rats

Acta Neurol Scand. 1997 Mar;95(3):140-6. doi: 10.1111/j.1600-0404.1997.tb00085.x.

Abstract

Glutamate receptor antagonists are protective in animal models of focal cerebral ischemia. Lamotrigine (3,5-diamino-6-[2,3-dichlorophenyl]-1,2, 4-triazine) is an anticonvulsant drug that blocks voltage-gated sodium channels and inhibits the ischemia-induced release of glutamate. Experiments in primary neuronal cultures implicate nitric oxide (NO) as a mediator of glutamatergic neurotoxicity acting via N-Methyl-D-Aspartate (NMDA) receptors. The effect of glutamate release inhibitor, Lamotrigine upon NO and cGMP production has been examined in focal cerebral ischemia in rats. Focal cerebral ischemia was produced by the permanent occlusion of right middle cerebral artery (MCA) in urethane anesthetized rats. A number of indicators of brain NO production (nitrite, cGMP) were determined in ipsilateral and contralateral cerebral cortex and cerebellum after 0, 10, 60 min of focal cerebral ischemia. The same parameters were measured in rats treated with Lamotrigine (20 mg/kg, i.p.) 30 min before or just after the occlusion of the right MCA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacology*
  • Anticonvulsants / therapeutic use*
  • Brain Ischemia / physiopathology*
  • Cerebellum / chemistry
  • Cerebellum / drug effects*
  • Cerebellum / physiopathology
  • Cerebral Arteries / physiopathology
  • Cerebral Cortex / chemistry
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / physiopathology
  • Cyclic GMP / analysis
  • Cyclic GMP / metabolism*
  • Excitatory Amino Acid Antagonists
  • Functional Laterality
  • Lamotrigine
  • Male
  • Nitric Oxide / analysis
  • Nitric Oxide / metabolism*
  • Radioimmunoassay
  • Rats
  • Receptors, Glutamate / drug effects
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Triazines / administration & dosage
  • Triazines / pharmacology*

Substances

  • Anticonvulsants
  • Excitatory Amino Acid Antagonists
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Triazines
  • Nitric Oxide
  • Cyclic GMP
  • Lamotrigine