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

doi:10.1016/0014-2999(89)90060-5

European Journal of Pharmacology

Volume 166, Issue 2, 18 July 1989, Pages 201-211

https://doi.org/10.1016/0014-2999(89)90060-5 Get rights and content

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 μmol/kg (i.p.); phencyclidine, ED₅₀ = 14 nmol (i.c.v.); 1.9 μmol/kg (i.p.); dextrorphan, ED₅₀ = 35 nmol (i.c.v.); 18.5 μmol/kg (i.p.); tiletamine, ED₅₀ = 40 nmol (i.c.v.); 5.6 μmol/kg (i.p.); SKF-10047, ED₅₀ = 50 nmol (i.c.v.); 23.5 μmol/kg (i.p.); dextromethorphan, ED₅₀ = 70 nmol (i.c.v.); 28.0 μmol/kg (i.p.); ketamine, ED₅₀ = 110 nmol (i.c.v.); 15.5 μmol/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.

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

Abstract

Toxicol. Appl. Pharmacol.

Brain Res.

European J. Pharmacol.

European J. Pharmacol.

Neurosci. Lett.

Pharmacol. Biochem. Behav.

Brain Res.

European J. Pharmacol.

European J. Pharmacol.

Brain Res.

Brain Res.

Brain Res.

Neuropharmacology

Biochem. Pharmacol.

Neurosci. Lett.

Ann. Neurol.

Epilepsy Res.

Life Sci.

Brain Res.

Life Sci.

Brain Res.

Brain Res.

Neuropharmacology

NMDA discriminative stimuli are antagonized by competitive NMDA antagonists, PCP-type compounds and kappa agonists

The distribution of [3H]-dextromethorphan binding sites in rat brain differs from that of NMDA sites

Ketamine effects on local cerebral blood flow and metabolism in the rat

J. Cereb. Blood Flow Metab.

The distribution of [³H]-dextromethorphan binding sites in rat brain differs from that of NMDA sites