title: Role of nitric oxide in additive anticonvulsant effects of agmatine and morphine.
abstract: The anticonvulsant effects of agmatine, an endogenous polyamine and a metabolite of l-arginine, have been shown in various experimental seizure models. Agmatine also potentiates the anti-seizure activity of morphine. The present study aimed to investigate a possible involvement of nitric oxide (NO) pathway in the protection by agmatine and morphine co-administration against pentylenetetrazole (PTZ) -induced seizure in male mice. To this end, the thresholds for the clonic seizures induced by the intravenous administration of PTZ, a GABA antagonist, were assessed. Intraperitoneal administration of morphine at lower dose (1mg/kg) increased the seizure threshold. Also intraperitoneal administration of agmatine (5 and 10mg/kg) increased the seizure threshold significantly. Combination of subeffective doses of morphine and agmatine led to potent anticonvulsant effects. Non-effective doses of morphine (0.1 and 0.5mg/kg) were able to induce anticonvulsant effects in mice pretreated with agmatine (3mg/kg). Concomitant administration of either the non-selective nitric oxide synthase (NOS) inhibitor L-NAME (1, 5mg/kg, i.p.) or the selective NOS inhibitor 7-NI (15, 30mg/kg, i.p.), with an ineffective combination of morphine (0.1mg/kg) plus agmatine (1mg/kg) produced significant anticonvulsant impacts. Moreover, the NO precursor, l-arginine (30, 60mg/kg, i.p.), inhibited the anticonvulsant action of agmatine (3mg/kg) plus morphine (0.5mg/kg) co-administration. Our results indicate that pretreatment of animals with agmatine enhances the anticonvulsant effects of morphine via a mechanism which may involve the NO pathway.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Borna
authors.initials: B
authors.lastname: Payandemehr
authors.forename: Reza
authors.initials: R
authors.lastname: Rahimian
authors.forename: Arash
authors.initials: A
authors.lastname: Bahremand
authors.forename: Ali
authors.initials: A
authors.lastname: Ebrahimi
authors.forename: Seyedehpariya
authors.initials: S
authors.lastname: Saadat
authors.forename: Peiman
authors.initials: P
authors.lastname: Moghaddas
authors.forename: Kaveh
authors.initials: K
authors.lastname: Fadakar
authors.forename: Hoda
authors.initials: H
authors.lastname: Derakhshanian
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000376:Agmatine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants; D001120:Arginine / Q000494:pharmacology; D003292:Convulsants; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D000376:Agmatine; D009020:Morphine; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D019331:NG-Nitroarginine Methyl Ester; D010433:Pentylenetetrazole
keywords: Agmatine; Mice; Morphine; Nitric oxide; Seizure