Claeson P, Zygmunt P, Högestätt E D
Department of Pharmacognosy, Uppsala University, Sweden.
Pharmacol Toxicol. 1991 Sep;69(3):173-7. doi: 10.1111/j.1600-0773.1991.tb01293.x.
(+)-T-Cadinol is a sesquiterpene with smooth muscle relaxing properties. In the isolated rat aorta, T-cadinol relaxed contractions induced by 60 mM K+ in a concentration-dependent fashion. The dihydropyridine calcium antagonist nimodipine was approximately 4,000 times more potent than T-cadinol. While both drugs nearly abolished the K(+)-induced contractions, they only partially relaxed contractions induced by phenylephrine. The relaxation induced by T-cadinol and nimodipine in K(+)-contracted aortic rings, was completely reversed by the calcium channel activator Bay K8644. In aortic preparations partially depolarized by 20 mM K+, Bay K8644 induced a concentration-dependent contraction. Nimodipine shifted the Bay K8644 concentration-response curve to the right in a parallel manner, consistent with a competitive mode of inhibition. T-cadinol at concentrations less than 10(-3.5) M also produced a right-ward shift of the Bay K8644 concentration-response curve with a maintained maximum response. However, the highest T-cadinol concentration used 10(-3.5 M) significantly reduced the maximum response. In conclusion, although T-cadinol and nimodipine display marked structural differences, their pharmacological profiles of action have several features in common, suggesting that T-cadinol is a calcium antagonist, possibly interacting with the dihydropyridine binding sites on the calcium channels.
（+）-T-杜松醇是一种具有平滑肌舒张特性的倍半萜。在离体大鼠主动脉中，T-杜松醇以浓度依赖性方式舒张由60 mM K⁺诱导的收缩。二氢吡啶类钙拮抗剂尼莫地平的效力比T-杜松醇强约4000倍。虽然两种药物几乎都消除了K⁺诱导的收缩，但它们仅部分舒张了去氧肾上腺素诱导的收缩。T-杜松醇和尼莫地平在K⁺收缩的主动脉环中诱导的舒张，被钙通道激活剂Bay K8644完全逆转。在由20 mM K⁺部分去极化的主动脉制剂中，Bay K8644诱导浓度依赖性收缩。尼莫地平以平行方式将Bay K8644浓度-反应曲线向右移动，这与竞争性抑制模式一致。浓度低于10⁻³·⁵ M的T-杜松醇也使Bay K8644浓度-反应曲线向右移动，同时最大反应保持不变。然而，所使用的最高T-杜松醇浓度10⁻³·⁵ M显著降低了最大反应。总之，虽然T-杜松醇和尼莫地平显示出明显的结构差异，但它们的药理学作用特征有几个共同之处，表明T-杜松醇是一种钙拮抗剂，可能与钙通道上的二氢吡啶结合位点相互作用。
