In the rat maximal dentate activation model of partial complex epilepsy, the anticonvulsant activity of levetiracetam is modulated by nitric oxide-active drugs.
The effects of nitric oxide-active drugs on the anticonvulsant action of the antiepileptic drug levetiracetam in an experimental model of partial complex seizures named maximal dentate gyrus activation were studied in rats. Levetiracetam was given alone or in combination with 7-nitroindazole, a preferential inhibitor of neuronal nitric oxide synthase, or with L: -arginine, the precursor of nitric oxide synthesis. The maximal dentate activation parameters were the time of latency and the durations of maximal dentate activation and afterdischarge responses. The administration of levetiracetam showed an anticonvulsant effect that was increased when given in combination with 7-nitroindazole. The co-administration of levetiracetam and L: -arginine, which is pro-convulsant, did not significantly modify all the parameters. The present results indicate that the acute administration of levetiracetam, at the lower effective dose, exerts an efficacious inhibitory effect on the severity of maximal dentate activation seizures. Levetiracetam-induced antiepileptic effect is significantly increased by the simultaneous inhibition of neuronal nitric oxide synthase.
Sardo
Pierangelo
P
Sezione di Fisiologia Umana G. Pagano, Dipartimento di Medicina Sperimentale, Università degli Studi di Palermo, Corso Tukory, 129, Palermo 90134, Italy.
D'Agostino
Stefania
S
Rizzo
Valerio
V
Carletti
Fabio
F
Lonobile
Gioacchino
G
Ferraro
Giuseppe
G
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017029:Epilepsy, Complex Partial / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D007191:Indazoles / Q000494:pharmacology; D000077287:Levetiracetam; D008297:Male; D009569:Nitric Oxide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007191:Indazoles; D009569:Nitric Oxide; D000077287:Levetiracetam; D001120:Arginine; D052248:Nitric Oxide Synthase Type I; C080122:7-nitroindazole; D010889:Piracetam