腈双吡啉对离体血管舒张的机理

腈双吡啉是从氨利酮与米利酮的合成衍生物中筛选出的强心扩血管药,离体实验表明它能拮抗高K~+、去甲肾上腺素(NE)收缩家兔主动脉环的作用,使NE,CaCl_2的量效曲线右移;在高浓度时降低最大收缩效应。它能增强钙调蛋白拮抗剂拮抗NE引起的家兔主动脉环收缩。结果表明它对NE收缩离体血管的量效曲线不同于选择性阻断α受体的药物妥拉唑啉的作用,也不同于典型的钙拮抗剂维拉帕米的作用,而可能是钙调蛋白的非竞争性拮抗剂。

Mechanism of vascular effects of 5-cyano-6-(4-morpho linyl)-3-4'-dipyridine in vitro

Aimed to develop more potent and less toxic inotropic agents, 5-cyano-6 (4-morpholinyl)-3, 4'-dipyridine (CMDP) wassynthesized as one of the milrinone analogues by Tianjin Institute of Pharmaceutical Research and was screened as a potent vasodila tor. The present study focused on its mecha nism of vascular effects in vitro. The data showed that CMDP(10μM-lmM) antagonized the contraction of isolated aortic ring, induced by norepinephrine (NE, 10 nM-10 μM), KC1 (40mM) and CaCl2 (0.1-10mM), and shifted the dose-response curves to the right in dose-dependent manner. In higher concentration (above 0.5-1 mM) it also depressed the maximal efficacy of contractions. In comparison with the pattern of dose response curves of tolazoline or verapamil on the NE induced aortic vessel contraction, CMDP neither behaved as a typical alpha receptor blocker nor a specific calcium an-tagonist. However, it significantly and dose dependently potentiated the calmodulin antagonistic action of trifluoperazine (TFP) on the NE contracted aorta of rabbit in vitro. It also depressed the maximal efficacy of contraction induced by NE. It is suggested that the vascular effects of CMDP may be attri butted to the noncompetitive antagonistic action on calmodulin.