Distinct effects of N omega-nitro-L-arginine on seizures induced by several drugs in mice.
A potent nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine (L-NA), suppressed tonic seizure elicited by pentylenetetrazol (PTZ; 100 mg/kg, SC) in a dose-related manner (25 to 100 mg/kg, IP), but had no effect on clonic seizure. The effect was most potent at 1 h after the administration of L-NA. L-NA (100 mg/kg, IP) suppressed clonic seizure as well as tonic seizure in bicuculline-treated (3.0 or 4.5 mg/kg, SC) mice. However, it did not affect seizures elicited by picrotoxin (2.0 to 6.0 mg/kg, SC). On the other hand, N-methyl-DL-aspartate (NMDLA; 300 mg/kg or 350 mg/kg, IP) induced clonic seizure, but tonic seizure was not always noted. All mice with clonic and tonic seizures died, and some mice with clonic seizure died without accompanying tonic seizure. L-NA did not influence NMDLA-induced seizures, but it appeared to enhance NMDLA lethality, though without statistical significance. These findings suggest distinct roles of NO in seizures induced by different drugs in mice.
Hara
S
S
Department of Forensic Medicine, Tokyo Medical College, Japan.
Kuriiwa
F
F
Iwata
N
N
Mukai
T
T
Kano
S
S
Endo
T
T
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010433:Pentylenetetrazole / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced*; D013997:Time Factors
D001120:Arginine; D001640:Bicuculline; D010433:Pentylenetetrazole; D010852:Picrotoxin