title: Anticonvulsant effects of cyclosporin A on pentylenetetrazole-induced seizure and kindling: modulation by nitricoxidergic system.
abstract: Cyclosporin A (CsA) is known to decrease nitric oxide (NO) release in the nervous system. The present study was aimed at investigating the effects of acute administration of CsA on pentylenetetrazole (PTZ)-induced seizure threshold and latency and probable modulation of these effects by NO synthesis substrate L-arginine, and NO synthesis inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME) or aminoguanidine. Moreover, the effect of CsA per se or concomitant with L-arginine on the development of PTZ-induced kindling was assessed. CsA (0.05, 1, 5, 10 and 20 mg/kg, s.c.) dose-dependently increased PTZ-induced clonic seizure threshold and the latency for onset of myoclonic jerks, clonic seizures and clonic-tonic generalized seizures following PTZ administration. L-NAME (10 and 30 mg/kg, i.p.) but not aminoguanidine (50 and 100 mg/kg, i.p.) potentiated the anticonvulsant effects of CsA (1 and 10 mg/kg). L-arginine (60, 100 and 200 mg/kg, i.p.) inhibited the anticonvulsant effects of CsA (20 mg/kg) in a dose-related manner. The inhibitory effect of L-arginine on CsA-induced alterations of seizure threshold and latency was blocked by L-NAME but not with aminoguanidine. CsA (20 mg/kg) significantly inhibited the development of PTZ kindling and decreased the seizure intensity as tested by a challenge dose of PTZ. Pretreatment with L-arginine (60 mg/kg) reversed the inhibitory effects of CsA on kindling development. It was concluded that CsA exerts some anticonvulsant properties that may be due to its inhibition of nitric oxide synthesis.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
authors.forename: Houman
authors.initials: H
authors.lastname: Homayoun
authors.forename: Simin
authors.initials: S
authors.lastname: Khavandgar
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001120:Arginine / Q000494:pharmacology; D003292:Convulsants; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000187:drug effects*; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D004791:Enzyme Inhibitors; D006146:Guanidines; D009569:Nitric Oxide; D016572:Cyclosporine; D001120:Arginine; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester; D010433:Pentylenetetrazole