Simon L, Ghaleh B, Puybasset L, Giudicelli J F, Berdeaux A
Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France.
J Pharmacol Exp Ther. 1995 Nov;275(2):659-66.
The effects of (7,8-dimethoxy 3-[3-([(1S)-(4,5-dimethoxybenzocyclobutan-1-yl)methyl]methylamino) - propyl]1,3,4,5-tetrahydro-2H-benzapin 2-one hydrochloride) (S 16257), a new bradycardic agent acting through inhibition of the hyperpolarization-activated I(f) current in the sino-atrial node, on arterial blood pressure, cardiac output, left ventricular pressure and dP/dt, epicardial coronary artery diameter and coronary blood flow velocity were investigated at graded doses (0.1 to 1 mg/kg) and compared to those of propranolol (1 mg/kg) and saline in chronically instrumented conscious dogs. At rest, S 16257 induced a dose-dependent bradycardia that was significant at 0.5 (-16% +/- 3%) and 1 mg/kg (-23% +/- 3%). At 0.5 mg/kg, S 16257 decreased both resting HR and treadmill exercise-induced tachycardia to a similar extent as propranolol. However, in contrast to propranolol, S 16257 (0.5 mg/kg) did not affect the increase in mean coronary blood flow velocity and the decrease in coronary vascular resistance observed during a control exercise performed under saline. In addition, S 16257 did not affect resting epicardial coronary artery diameter and only attenuated its increase during exercise, whereas propranolol reduced it at rest and maintained a significant constriction of these large vessels throughout the exercise period. Propranolol, but not S 16257, decreased left ventricular dP/dt at each stage of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了新型心动过缓药物（7,8 - 二甲氧基 - 3 - [3 - ([(1S)-(4,5 - 二甲氧基苯并环丁烷 - 1 - 基)甲基]甲基氨基) - 丙基] - 1,3,4,5 - 四氢 - 2H - 苯并氮卓 - 2 - 酮盐酸盐）（S 16257）在慢性植入仪器的清醒犬体内，通过抑制窦房结超极化激活的I(f)电流对动脉血压、心输出量、左心室压力和dP/dt、心外膜冠状动脉直径和冠状动脉血流速度的影响。以分级剂量（0.1至1 mg/kg）给药，并与普萘洛尔（1 mg/kg）和生理盐水在相同条件下进行比较。静息时，S 16257引起剂量依赖性心动过缓，在0.5（-16%±3%）和1 mg/kg（-23%±3%）时具有显著性。在0.5 mg/kg时，S 16257降低静息心率和跑步机运动诱导的心动过速的程度与普萘洛尔相似。然而，与普萘洛尔不同，S 16257（0.5 mg/kg）不影响生理盐水对照运动期间观察到的平均冠状动脉血流速度增加和冠状动脉血管阻力降低。此外，S 16257不影响静息时的心外膜冠状动脉直径，仅减弱运动期间其扩张，而普萘洛尔在静息时使其缩小，并在整个运动期间维持这些大血管的显著收缩。普萘洛尔而非S 16257在运动各阶段降低左心室dP/dt。（摘要截断于250字）
