Agmatine exerts anticonvulsant effect in mice:: modulation by α2-adrenoceptors and nitric oxide
Agmatine exerts anticonvulsant effect in mice:: modulation by α2-adrenoceptors and nitric oxide
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DOI：
10.1016/s0028-3908(03)00199-0
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发表时间：
2003-09-01
影响因子：
4.7
通讯作者：
Dehpour, AR
中科院分区：
文献类型：
--
作者：
Demehri, S;Homayoun, H;Dehpour, AR
研究了内源性多胺代谢物--胍丁胺对小鼠癫痫敏感性的影响。急性腹腔注射胍丁胺(5、10、20、40 mg/kg)对戊四氮(PTZ)诱导的癫痫发作有明显的抑制作用，且呈剂量依赖关系。该抗惊厥作用高峰出现在给药后45min。我们进一步研究了α(2)-肾上腺素能受体和L-精氨酸/NO通路可能参与胍丁胺的这一作用。α(2)-肾上腺素能受体拮抗剂育亨宾(0.5-2 mg/kg)可剂量依赖性地阻断胍丁胺的抗惊厥作用。一氧化氮合酶底物L-精氨酸(60 mg/kg)可抑制胍丁胺的抗惊厥作用，这种作用可被一氧化氮合酶抑制剂N(G)-硝基-L-精氨酸(L-NAME，30 mg/kg)显著逆转，提示L-精氨酸的作用机制是NO依赖的。我们进一步研究了胍丁胺(1或5 mg/kg)和L-NAME(10 mg/kg)之间可能的相加作用。L-NAME(10 mg/kg)与胍丁胺(5 mg/kg而不是1 mg/kg)合用可显著提高对癫痫的保护作用。此外，联合应用小剂量育亨宾(0.5 mg/kg)和L精氨酸(30 mg/kg)也可显著降低胍丁胺的抗惊厥作用。综上所述，目前的数据表明胍丁胺可能在癫痫治疗中有潜在的用途。(C)2003爱思唯尔有限公司。保留所有权利。
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. (C) 2003 Elsevier Ltd. All rights reserved.