The new competitive NMDA receptor antagonist CGP 40116 inhibits pilocarpine-induced limbic motor seizures and unconditioned motor behaviour in the mouse.
The biologically active enantiomer (CGP 40116) of the new competitive N-methyl-D-aspartate (NMDA) receptor antagonist CGP 37849 was investigated for its effects on pilocarpine-induced limbic motor seizures and unconditioned motor behaviour in the mouse. CGP 40116 (1-8 mg/kg IP) reduced the incidence and severity of pilocarpine-induced motor seizures, although the overall effect was weak. In contrast to the noncompetitive NMDA antagonist MK 801, there were no signs of CGP 40116 producing a proconvulsant response in this model. In the nonhabituated mouse, MK 801 promoted hyperlocomotion at low doses and hypolocomotion and ataxia at high doses, while CGP 40116 dose-dependently suppressed motor behaviour. Because CGP 40116 and MK 801 exert opposite effects on the seizure threshold to pilocarpine and differentially alter species-typical behaviours in the mouse, it is suggested that different populations of NMDA receptors may mediate their effects. The indivisibility of seizure suppression and motor impairment noted previously with noncompetitive NMDA antagonists such as MK 801 appears also to apply to the new generation competitive NMDA antagonist CGP 40116.
Starr
M S
MS
Department of Pharmacology, School of Pharmacy, London, UK.
Starr
B S
BS
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006120:Grooming / Q000187:drug effects; D008032:Limbic System / Q000503:physiopathology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D010862:Pilocarpine / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*
D016194:Receptors, N-Methyl-D-Aspartate; D010862:Pilocarpine; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate