Interaction between GABAergic anticonvulsants and the NMDA receptor antagonist MK 801 against MES- and picrotoxin-induced convulsions in rats

Shrinivas K. Kulkarni, Maharaj K. Ticku

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The interaction between GABAergic (barbiturates, diazepam, ethanol) and other (phenytoin) anticonvulsants and the N-methyl-D-aspartate (NMDA) receptor antagonist MK 801 in protecting rats against maximal electroshock (MES)- and picrotoxin-induced (10 mg/kg) convulsions was studied. MK 801 (0.1 to 5 mg/kg) showed anticonvulsant responses against MES-induced convulsions in a dose dependent manner, higher doses showing severe muscle relaxation, motor incoordination, and anticonvulsant action. It also produced stereotypic head movement, circling behavior, and affected locomotion. When subanticonvulsant dose (1 mg/kg) of MK 801 was simultaneously administered with subprotective doses of GABAergic anticonvulsants, it significantly potentiated the effects of barbiturates, as compared to other agents. At 1 mg/kg, MK 801 did not offer protection against tonic convulsions though protected (100%) the animals from mortality due to picrotoxin-induced convulsions. It potentiated the effect of a subprotective dose (5 mg/kg) of pentobarbital, but not of diazepam, against tonic convulsions. However, no mortality was observed in either group. The antiglutamate action of barbiturates, particularly that of pentobarbital, may contribute to the observed potentiating response between pentobarbital and MK 801.

Original languageEnglish (US)
Pages (from-to)1317-1323
Number of pages7
JournalLife Sciences
Volume44
Issue number18
DOIs
StatePublished - 1989

Keywords

  • barbiturates
  • electroshock seizures
  • GABAergic anticonvulsants
  • MK 801
  • NMDA antagonists

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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