Anticonvulsant activity of MK-801 and nimodipine alone and in combination against pentylenetetrazole and strychnine.
The effects of the N-methyl-D-aspartate receptor antagonist MK-801 and the dihydropyridine calcium channel antagonist nimodipine were assessed for their anticonvulsant activity alone and in combination against clonic convulsions to pentylenetetrazole (PTZ) and strychnine (STR) in mice. Nimodipine (2-20 mg/kg) and MK-801 (0.1 and 0.5 mg/kg) did not affect the number of mice displaying clonic convulsions to PTZ. However, nimodipine in a dose-dependent manner increased (100%) the latency to clonic convulsions and lethality (mortality from tonic extension convulsions and respiratory failure) following PTZ. In contrast, MK-801 did not increase the latency to PTZ convulsions, but prevented the lethal effects of PTZ. When combined, MK-801 and nimodipine produced a significant reduction in the number of animals (40-60%) displaying PTZ convulsions and a greater increase in the latency to PTZ convulsions than did nimodipine alone. In contrast, MK-801 decreased the onset time, and increased the severity of STR convulsions. A combination of MK-801 and nimodipine which afforded significant protection against PTZ convulsions did not affect STR convulsions. These findings suggest that MK-801 and nimodipine, while possessing significant anticonvulsant activity on their own, produce a potent anticonvulsant synergism against PTZ but not STR.
O'Neill
S K
SK
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Bolger
G T
GT
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D009553:Nimodipine / Q000494:pharmacology*; D010433:Pentylenetetrazole / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced*; D013331:Strychnine / Q000494:pharmacology*
D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D009553:Nimodipine; D016291:Dizocilpine Maleate; D013331:Strychnine; D010433:Pentylenetetrazole