Nitric oxide and convulsions in 4-aminopyridine-treated mice

Eur J Pharmacol. 2002 Feb 15;437(1-2):47-53. doi: 10.1016/s0014-2999(01)01600-4.

Abstract

We studied whether N(G)-nitro-L-arginine (NNA), an inhibitor of nitric oxide (NO) synthase as well as L-arginine and molsidomine, two agents elevating NO, influenced convulsions caused by 4-aminopyridine, a K+ channel blocker in mice. NNA, in a dose known to decrease level of NO (40 mg x kg(-1)), enhanced the seizure susceptibility to intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) 4-aminopyridine. L-arginine (500 mg x kg(-1)) and molsidomine (20 mg x kg(-1)) alone did not influence 4-aminopyridine-induced seizure activity. Surprisingly, the proconvulsant effect of NNA upon clonic and tonic seizures was potentiated by molsidomine (20 mg x kg(-1)). No influence of L-arginine on the proconvulsant effect of NNA was found. Taking into account the proconvulsant effect of NNA, an involvement of NO-mediated events in the mechanism of convulsive activity of 4-aminopyridine might be postulated. However, the ineffectiveness of L-arginine and molsidomine to suppress the convulsive activity of 4-aminopyridine as well as a paradoxical potentiation of the proconvulsant effect of NNA by molsidomine seem to exclude the impact of NO pathway on 4-aminopyridine-induced convulsions in mice. Our data suggest that the proconvulsant effect of NNA in this seizure model is caused by other, not related to NO, mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / toxicity*
  • Animals
  • Arginine / pharmacology
  • Behavior, Animal / drug effects
  • Enzyme Inhibitors / pharmacology
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Lethal Dose 50
  • Male
  • Mice
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitroarginine / pharmacology
  • Seizures / chemically induced*
  • Seizures / prevention & control

Substances

  • Enzyme Inhibitors
  • Nitroarginine
  • Nitric Oxide
  • Arginine
  • 4-Aminopyridine
  • Nitric Oxide Synthase