Agmatine exerts anticonvulsant effect in mice: modulation by alpha 2-adrenoceptors and nitric oxide.
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 alpha(2)-adrenoceptors and L-arginine/NO pathway in this effect of agmatine. The alpha(2)-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 N(G)-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.
Demehri
Shadpour
S
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
Homayoun
Houman
H
Honar
Hooman
H
Riazi
Kiarash
K
Vafaie
Kourosh
K
Roushanzamir
Farshad
F
Dehpour
Ahmad Reza
AR
D058669:Adrenergic alpha-2 Receptor Antagonists; D000376:Agmatine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology
D058669:Adrenergic alpha-2 Receptor Antagonists; D000927:Anticonvulsants; D018341:Receptors, Adrenergic, alpha-2; D009569:Nitric Oxide; D000376:Agmatine