Demehri Shadpour, Homayoun Houman, Honar Hooman, Riazi Kiarash, Vafaie Kourosh, Roushanzamir Farshad, Dehpour Ahmad Reza
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
Neuropharmacology. 2003 Sep;45(4):534-42. doi: 10.1016/s0028-3908(03)00199-0.
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.
在小鼠中研究了内源性多胺代谢产物胍丁胺对癫痫易感性的影响。腹腔注射胍丁胺（5、10、20、40mg/kg）对戊四氮（PTZ）诱导的癫痫发作具有显著的剂量依赖性抑制作用。这种抗惊厥作用的峰值出现在胍丁胺给药后45分钟。我们进一步研究了α₂-肾上腺素能受体和L-精氨酸/一氧化氮途径在胍丁胺这一作用中的可能参与情况。α₂-肾上腺素能受体拮抗剂育亨宾（0.5 - 2mg/kg）可剂量依赖性地阻断胍丁胺的抗惊厥作用。一氧化氮合酶（NOS）底物L-精氨酸（60mg/kg）抑制了胍丁胺的抗惊厥特性，而NOS抑制剂N⁰-硝基-L-精氨酸（L-NAME，30mg/kg）可显著逆转这一作用，这意味着L-精氨酸的作用存在一氧化氮依赖性机制。我们进一步研究了胍丁胺（1或5mg/kg）与L-NAME（10mg/kg）之间可能的相加作用。与单独使用每种药物相比，L-NAME（10mg/kg）与胍丁胺（5mg/kg而非1mg/kg）联合使用可诱导更高水平的癫痫保护作用。此外，较低剂量的育亨宾（0.5mg/kg）和L-精氨酸（30mg/kg）联合使用也显著降低了胍丁胺的抗惊厥作用。总之，目前的数据表明胍丁胺在癫痫治疗中可能具有潜在用途。
