Anticonvulsant activity of a novel NMDA/glycine site antagonist, MDL 104,653, against kindled and sound-induced seizures.

Abstract

MDL 104,653 (3-phenyl-4-hydroxy-7-chloro-quinolin-2(1H)-one), acts as an antagonist at the glycine site of the NMDA receptor. MDL 104,653 protects against sound-induced clonic seizures in DBA/2 mice following intracerebroventricular (ED50 = 19.1 nmol, 30 min), intraperitoneal (i.p.; ED50 = 6.1 mumol/kg, 45 min), or oral (ED50 = 23.0 mumol/kg, 2 h) administration. Optimal protection by MDL 104,653 was observed 15-60 min after i.p. administration, and the therapeutic index, as assessed by rotarod performance, was 4.0 at 45 min after i.p. administration. Fully amygdala-kindled motor seizures in rats were significantly reduced at 15, 30 and 60 min, and the duration of the after-discharge was significantly shortened at 30 min after the i.p. administration of 74 mumol/kg MDL 104,653. A lower dose of MDL 104,653 (37 mumol/kg) had no significant effect on either motor seizures or after-discharge duration. The rate of amygdala kindling was also significantly retarded following the daily administration of 56 mumol/kg MDL 104,653 (1 times daily for 6 days; i.p. 30 min before kindling stimulus).

• Authors: A G Chapman, N Dürmüller, B L Harrison, B M Baron, N Parvez, B S Meldrum
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 274 Issue 1-3 Pg. 83-8 (Feb 14 1995) ISSN: 0014-2999 [Print] Netherlands
• PMID: 7768284 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Quinolones
• Receptors, N-Methyl-D-Aspartate
• 3-phenyl-4-hydroxy-7-chloroquinolin-2(1H)-one

Topics

• Administration, Oral
• Amygdala (drug effects, physiology)
• Analysis of Variance
• Animals
• Behavior, Animal (drug effects)
• Dose-Response Relationship, Drug
• Female
• Injections, Intraperitoneal
• Injections, Intraventricular
• Kindling, Neurologic (drug effects)
• Male
• Mice
• Mice, Inbred DBA
• Quinolones (administration & dosage, pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Seizures (prevention & control)
• Sound (adverse effects)