Non-competitive N-methyl-D-aspartate antagonists protect against sound-induced seizures in DBA/2 mice

Eur J Pharmacol. 1989 Jul 18;166(2):201-11. doi: 10.1016/0014-2999(89)90060-5.

Abstract

Non-competitive antagonists of the N-methyl-D-aspartate (NMDA) receptor have been evaluated as anticonvulsants against sound-induced seizures in DBA/2 mice. The ED50 values for protection against sound-induced clonic seizures 15 min following the intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration are: MK-801, ED50 = 0.5 nmol (i.c.v.); 0.14 mumol/kg (i.p.); phencyclidine, ED50 = 14 nmol (i.c.v.); 1.9 mumol/kg (i.p.); dextrorphan, ED50 = 35 nmol (i.c.v.); 18.5 mumol/kg (i.p.); tiletamine, ED50 = 40 nmol (i.c.v.); 5.6 mumol/kg (i.p.); SKF-10047, ED50 = 50 nmol (i.c.v.); 23.5 mumol/kg (i.p.); dextromethorphan, ED50 = 70 nmol (i.c.v.); 28.0 mumol/kg (i.p.); ketamine, ED50 = 110 nmol (i.c.v.); 15.5 mumol/kg (i.p.). The anticonvulsant effects of ketamine and tiletamine are of short duration (10-30 min), whereas the anticonvulsant effects of MK-801 and dextromethorphan last for 45 min or longer. The effects of phencyclidine, SKF-10047 and dextrorphan are of intermediate duration. Mild to moderate behavioural excitation is associated with the anticonvulsant activity of all the non-competitive NMDA antagonists. For MK-801, phencyclidine, dextrorphan, SKF-10047 and ketamine there is a close correlation between their relative anticonvulsant potencies and their potencies for displacing [3H]MK-801. The anticonvulsant effect is likely to be primarily mediated via NMDA antagonism at the PCP/MK-801 site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Anticonvulsants*
  • Aspartic Acid / antagonists & inhibitors
  • Aspartic Acid / pharmacology
  • Behavior, Animal / drug effects
  • Body Temperature / drug effects
  • Female
  • Male
  • Mice
  • Mice, Inbred DBA
  • N-Methylaspartate
  • Seizures / physiopathology
  • Seizures / prevention & control*
  • Time Factors

Substances

  • Anticonvulsants
  • Aspartic Acid
  • N-Methylaspartate