Anticonvulsant activity of 5,7DCKA, NBQX, and felbamate against some chemoconvulsants in DBA/2 mice.
The anticonvulsant effects of felbamate (10-300 mg/kg, intraperitoneally, IP), and those of two representative antagonists of the excitatory amino acid receptors, 5-7 dichlorokynurenic acid (5-7DCKA; 0.6-30 nmol/mouse, intracerebroventricularly, ICV), and 2, 3-dihydroxy-6 nitro-7-sulfamoylbenzo (F) quinoxoline (NBQX; 1.1-33.6 mg/kg, IP) were studied in the DBA/2 mice. All drugs protected the animals from sound-induced seizures. The drugs were also effective against seizures induced by stimulation of the excitatory amino acid receptor complex using the agonists N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5 methyl-4-isoxazolepropionic acid (AMPA). In separate studies, felbamate protected mice from seizures induced by ICV administration of the activator of dihydropyridine-sensitive calcium channels, methyl-1, 4-dihydro-2, 6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl) pyridine-5-carboxylate (Bay k 8644), with ED50 values of 26 and 46.9 mg/kg for tonus and clonus, respectively. Using Bay k 8644, NBQX (1-40 mg/kg IP) was uneffective, while 5,7DCKA (5-90 nmol/mouse, ICV) protected mice against tonus. Moreover, felbamate prevented seizures induced by blocking voltage-dependent K+ channels using alpha-dendrotoxin, with ED50 values of 22.6 mg/kg for tonus and of 34.8 mg/kg for clonus. Conversely, 5,7DCKA or NBQX did not significantly antagonize seizures induced by alpha-dendrotoxin. The present data indicate that felbamate is an effective anticonvulsant drug in DBA/2 mice with a broader anticonvulsant spectrum than 5,7DCKA and NBQX.
De Sarro
G
G
Department of Experimental and Clinical Medicine, School of Medicine, University of Reggio Calabria, Italy.
Ongini
E
E
Bertorelli
R
R
Aguglia
U
U
De Sarro
A
A
D000161:Acoustic Stimulation; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003292:Convulsants / Q000008:administration & dosage / Q000494:pharmacology*; D004597:Electroshock; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D000078328:Felbamate; D005260:Female; D007276:Injections, Intraventricular; D015640:Ion Channel Gating / Q000187:drug effects; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000187:drug effects; D048448:Phenylcarbamates; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011409:Propylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*
D000927:Anticonvulsants; D003292:Convulsants; D018691:Excitatory Amino Acid Antagonists; D048448:Phenylcarbamates; D015221:Potassium Channels; D011409:Propylene Glycols; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D007736:Kynurenic Acid; C066192:5,7-dichlorokynurenic acid; D000078328:Felbamate