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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.
AuthorsBorna Payandemehr, Reza Rahimian, Arash Bahremand, Ali Ebrahimi, Seyedehpariya Saadat, Peiman Moghaddas, Kaveh Fadakar, Hoda Derakhshanian, Ahmad Reza Dehpour
JournalPhysiology & behavior (Physiol Behav) Vol. 118 Pg. 52-7 (Jun 13 2013) ISSN: 1873-507X [Electronic] United States
PMID23685229 (Publication Type: Journal Article)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Anticonvulsants
  • Convulsants
  • Enzyme Inhibitors
  • Nitric Oxide
  • Agmatine
  • Morphine
  • Arginine
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • NG-Nitroarginine Methyl Ester
  • Pentylenetetrazole
Topics
  • Agmatine (administration & dosage, pharmacology)
  • Animals
  • Anticonvulsants
  • Arginine (pharmacology)
  • Convulsants
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors (pharmacology)
  • Epilepsy, Tonic-Clonic (chemically induced, prevention & control)
  • Male
  • Mice
  • Morphine (administration & dosage, pharmacology)
  • NG-Nitroarginine Methyl Ester (pharmacology)
  • Nitric Oxide (physiology)
  • Nitric Oxide Synthase (antagonists & inhibitors)
  • Nitric Oxide Synthase Type I (antagonists & inhibitors)
  • Pentylenetetrazole
  • Seizures (chemically induced, physiopathology, prevention & control)

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