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

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 α 2 -adrenoceptors and l -arginine/NO pathway in this effect of agmatine. The α 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.