Agmatine exerts anticonvulsant effect in mice: Modulation by α2-adrenoceptors and nitric oxide

Shadpour Demehri, Houman Homayoun, Hooman Honar, Kiarash Riazi, Kourosh Vafaie, Farshad Roushanzamir, Ahmad Reza Dehpour

Research output: Contribution to journalArticlepeer-review

Abstract

The effect of agmatine, an endogenous polyamine metabolite, on seizure susceptibility was investigated in mice. Acute intraperitoneal administration of agmatine (5, 10, 20, 40 mg/kg) had a significant and dose-dependent inhibitory effect on pentylenetetrazole (PTZ)-induced seizures. The peak of this anticonvulsant effect was 45 min after agmatine administration. We further investigated the possible involvement of the α2-adrenoceptors and L-arginine/NO pathway in this effect of agmatine. The α2-adrenoceptor antagonist, yohimbine (0.5-2 mg/kg), induced a dose-dependent blockade of the anticonvulsant effect of agmatine. The nitric oxide synthase (NOS) substrate, L-arginine (60 mg/kg), inhibited the anticonvulsant property of agmatine and this effect was significantly reversed by NOS inhibitor NG-nitro-L-arginine (L-NAME, 30 mg/kg), implying an NO-dependent mechanism for L-arginine effect. We further examined a possible additive effect between agmatine (1 or 5 mg/kg) and L-NAME (10 mg/kg). The combination of L-NAME (10 mg/kg) with agmatine (5 but not 1 mg/kg) induced a significantly higher level of seizure protection as compared with each drug alone. Moreover, a combination of lower doses of yohimbine (0.5 mg/kg) and L-arginine (30 mg/kg) also significantly decreased the anticonvulsant effect of agmatine. In conclusion, the present data suggest that agmatine may be of potential use in seizure treatment.

Original languageEnglish (US)
Pages (from-to)534-542
Number of pages9
JournalNeuropharmacology
Volume45
Issue number4
DOIs
StatePublished - Sep 2003
Externally publishedYes

Keywords

  • Agmatine
  • L-Arginine
  • L-NAME
  • Pentylenetetrazole
  • Yohimbine
  • α-Adrenergic

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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