Involvement of nitric oxide and nitric oxide synthase activity in anticonvulsive action.
The anticonvulsant drug Diazepam (DIA-2 mg/kg b. wt), the nitric oxide (NO) donor L-Arginine (L-Arg-2000 mg/kg b. wt) and the putative nitric oxide synthase (NOS) inhibitor N(G)-Nitro-L-Arginine methyl ester (L-NAME-50 mg/kg b. wt) were used to determine the role of endogenous NO on convulsions induced by picrotoxin (PCT-5 mg/kg b. wt) in rats. Rats given a convulsant dose of PCT (5 mg/kg b. wt) had convulsion and it suppresses the NOS activity and NO concentration in brain regions. The anticonvulsant L-Arg alone significantly increases the NO concentration and NOS activity in brain regions, but not diazepam. Whereas DIA, along with L-Arg, enhances the NO and NOS activity when compared to L-Arg alone. The combination of both OIA and L-Arg completely suppressed the convulsions. L-NAME alone had no effect to produce convulsions but it completely decreased NO concentration and NOS activity and potentiated the PCT convulsions. This was reverted by pre- and post treatment of DIA plus L-Arg indicating, the increased NO concentration and NOS activity in brain regions suppresses convulsions.
Jayakumar
A R
AR
Department of Pharmacology, Dr. A.L.M. Postgraduate Institute of Basic Medical Sciences, Taramani, Chennai, India.
Sujatha
R
R
Paul
V
V
Puviarasan
K
K
Jayakumar
R
R
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D003292:Convulsants; D003975:Diazepam / Q000494:pharmacology; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000502:physiology*; D010852:Picrotoxin; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*
D000927:Anticonvulsants; D001120:Arginine; D003292:Convulsants; D003975:Diazepam; D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D020030:Nitric Oxide Donors; D019001:Nitric Oxide Synthase; D010852:Picrotoxin