Further studies on anti- and proconvulsant effects of inhibitors of nitric oxide synthase in rodents.
We confirmed that the effects of inhibitors of nitric oxide (NO) synthase, such as Nomega-nitro-L-arginine methyl ester and Nomega-nitro-L-arginine, differ depending on several experimental factors. Both compounds but not their less active enantiomers delayed picrotoxin-induced clonus in mice yet increased the incidence of clonus following low-dose picrotoxin. Nomega-nitro-L-arginine methyl ester significantly reduced the latencies of both myoclonus and clonus in older but not younger Sprague-Dawley rats receiving pentylenetetrazol s.c. By contrast, there was no significant change in the latencies for myoclonus and clonus in Wistar rats (older and younger). However, when pentylenetetrazol was administered i.p. rather than s.c., Nomega-nitro-L-arginine methyl ester dramatically increased latencies of convulsive indicators, including tonus, in both Sprague-Dawley and Wistar rats. Nomega-nitro-L-arginine methyl ester also delayed tonus but not myoclonus or clonus in mice, regardless of the systemic route of administration of pentylenetetrazol. Both Nomega-nitro-L-arginine methyl ester and NG-nitro-L-arginine increased the tonic CD50 of pentylenetetrazol in mice and Nomega-nitro-L-arginine methyl ester delayed 4-aminopyridine-induced tonus. However, Nomega-nitro-L-arginine methyl ester reduced the tonic CD50 of both picrotoxin and 4-aminopyridine in mice and failed to suppress tonus following maximal electroshock. Evidently, inhibitors of NO synthase are not universally effective antitonic drugs.
Alexander
C B
CB
Neuronal Excitability Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1408, USA.
Ellmore
T M
TM
Kokate
T G
TG
Kirkby
R D
RD
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D010433:Pentylenetetrazole / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced
D000927:Anticonvulsants; D003292:Convulsants; D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010433:Pentylenetetrazole; D010852:Picrotoxin