选择性磷酸二酯酶抑制和体外和体内力量的新PDE5抑制剂伐地那非。

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Saenz de Tejada我Angulo J奎瓦斯P,费尔南德斯,蒙我,Allona, Lledo E, Korschen HG, Niewohner U,韩寒H,页面E,比肖夫E

选择性磷酸二酯酶抑制和体外和体内力量的新PDE5抑制剂伐地那非。

Int J单一研究》2001年10月,13 (5):282 - 90。

PubMed ID

11890515 (在PubMed

]

文摘

我们调查了效力,伐地那非的选择性磷酸二酯酶(pde)酶,它能够修改cGMP的新陈代谢,导致勃起阴茎的平滑肌松弛及其影响条件下体内的外源性一氧化氮(NO)刺激。PDE同功酶提取和纯化从人类血小板(PDE5)或牛来源(PDE 1、2、3、4和6)。这些PDE的抑制,伐地那非人类重组PDE的决心。能够加强NO-mediated放松和影响人类阴茎海绵体cGMP水平条体外测定,和erection-inducing活动是在有意识的兔子后口服和静脉注射剂量的硝普酸钠(SNP)。伐地那非的影响比较公认的PDE5抑制剂,西地那非(西地那非的值在括号中)。伐地那非专门抑制cGMP的水解PDE5的IC50 0.7海里(6.6海里)。相比之下,伐地那非的IC50 PDE1 180海里;为PDE6 11 nM;PDE2, PDE3 PDE4,超过1000海里。的比例相对于PDE5的IC50 PDE1 257 (60), PDE6 16 (7.4)。伐地那非显著增强人类小梁的SNP-induced放松平滑肌在3 nM(10海里)。 Vardenafil also significantly potentiated both ACh-induced and transmural electrical stimulation-induced relaxation of trabecular smooth muscle. The minimum concentration of vardenafil that significantly potentiated SNP-induced cGMP accumulation was 3 nM (30 nM). In vivo studies in rabbits showed that orally administered vardenafil dose-dependently potentiated erectile responses to intravenously administered SNP. The minimal effective dose that significantly potentiated erection was 0.1 mg/kg (1 mg/kg). The selectivity for PDE5, the potentiation of NO-induced relaxation and cGMP accumulation in human trabecular smooth muscle and the ability to enhance NO-induced erection in vivo indicate that vardenafil has the appropriate properties to be a potential compound for the treatment of erectile dysfunction. Vardenafil was more potent and selective than sildenafil on its inhibitory activity on PDE5.

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药物靶点

药物	目标	类	生物	药理作用	行动
伐地那非	cGMP-specific 3 ', 5 '环磷酸二酯酶	蛋白质	人类	是的	抑制剂	细节