Cleary L, Vandeputte C, Kelly J G, Docherty J R
Department of Physiology, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
Auton Autacoid Pharmacol. 2004 Jul;24(3):63-7. doi: 10.1111/j.1474-8673.2004.00317.x.
1 We have investigated the actions of the calcium entry blockers nifedipine, R-verapamil and S-verapamil in rat aorta, colon and vas deferens. 2 In aorta and colon, these agents produced concentration-dependent relaxations of KCl (80 mM)-induced contractions. In both tissues, the order of potency was nifedipine > S-verapamil > R-verapamil. However, nifedipine showed selectivity for aorta (potency ratio, colon/aorta: 4.36), S-verapamil showed no selectivity (0.62), but R-verapamil showed selectivity for colon (0.19). 3 In prostatic portions of rat vas deferens, nifedipine (10 microM) abolished the contraction to a single electrical stimulus, but R- and S-verapamil were without effect. In epididymal portions of rat vas deferens, R- and S-verapamil inhibited alpha1-adrenoceptor-mediated contractions to a single electrical stimulus at concentrations of 10 microM and above. 4 In conclusion, R-verapamil may prove useful as an intestinal selective calcium entry blocker in the treatment of intestinal disease with a hypermotility component, e.g. irritable bowel syndrome.
1我们研究了钙通道阻滞剂硝苯地平、R-维拉帕米和S-维拉帕米对大鼠主动脉、结肠和输精管的作用。2在主动脉和结肠中，这些药物可使氯化钾（80 mM）诱导的收缩产生浓度依赖性舒张。在这两种组织中，效力顺序为硝苯地平>S-维拉帕米>R-维拉帕米。然而，硝苯地平对主动脉具有选择性（效价比，结肠/主动脉：4.36），S-维拉帕米无选择性（0.62），而R-维拉帕米对结肠具有选择性（0.19）。3在大鼠输精管的前列腺部，硝苯地平（10 μM）可消除对单个电刺激的收缩反应，但R-和S-维拉帕米无此作用。在大鼠输精管的附睾部，R-和S-维拉帕米在浓度为10 μM及以上时可抑制α1肾上腺素能受体介导的对单个电刺激的收缩反应。4总之，R-维拉帕米可能作为一种肠道选择性钙通道阻滞剂，用于治疗具有运动亢进成分的肠道疾病，如肠易激综合征。
