Agmatine exerts anticonvulsant effect in mice: modulation by α2-adrenoceptors and nitric oxide
2003
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.
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