2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline enhances the protective activity of common antiepileptic drugs against maximal electroshock-induced seizures in mice.
NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline), a novel and selective AMPA antagonist, was tested to evaluate its influence upon anticonvulsant activity of common antiepileptic drugs in mice. NBQX (10, 20, 40 mg/kg, i.p.) had no influence upon the threshold for electroconvulsions. NBQX (10 mg/kg) enhanced the activity of anticonvulsant drugs decreasing their ED50S against maximal electroshock from 321 to 190 mg/kg for valproate, from 19.5 to 14.5 mg/kg for carbamazepine, from 31.0 to 21.4 mg/kg for phenobarbital, from 17.8 to 9.5 mg/kg for diphenylhydantoin and from 19.5 to 10.5 mg/kg for diazepam. In addition, NBQX (10 mg/kg) failed to impair motor performance and long-term memory determined in the chimney test and passive avoidance task. The combinations of NBQX (10 mg/kg) and carbamazepine, diphenylhydantoin or phenobarbital resulted in no adverse effects. Diazepam (10.5 mg/kg) alone impaired the motor performance and long-term memory and so it did when combined with NBQX. Also retention of the passive avoidance task and motor performance were impaired by valproate alone or given together with NBQX. Finally, NBQX (10 mg/kg) did not affect the plasma level of any antiepileptic drug. It is concluded that non-NMDA glutamate receptor blockade results in the considerable enhancement of the efficacy of common antiepileptic drugs.
Zarnowski
T
T
Department of Pharmacology, Medical School, Lublin, Poland.
Kleinrok
Z
Z
Turski
W A
WA
Czuczwar
S J
SJ
D000818:Animals; D000927:Anticonvulsants / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D001259:Ataxia / Q000139:chemically induced; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D004357:Drug Synergism; D004597:Electroshock; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D011810:Quinoxalines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012640:Seizures / Q000517:prevention & control*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000037:antagonists & inhibitors*
D000927:Anticonvulsants; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid