Diederen W, Kadatz R
Arzneimittelforschung. 1981;31(1a):146-50.
In anaesthetized dogs, 0.03--10 mg/kg 2-[(2-methoxy-4-methylsulfinyl)-phenyl]-1H-imidazo[4,5-b]pyridine (AR-L 115 BS) i.V. increased dp/dtmax by 3-221% and VCE by 1-196%. Threshold doses for a positive chronotropic effect were higher, beginning at 0.3 mg/kg and amounting to +70% at 10 mg/kg. Systemic blood pressure was not influenced significantly, whereas pulmonary pressure was lowered slightly at all doses and likewise left ventricular enddiastolic pressure at 3 and 10 mg/kg. Similar effects were observed in anaesthetized baboons at 0.1--5 mg/kg and in mini-pigs at 0.1--10 mg/kg i.v. Duration of the effect on contractility parameters was 20 to 100 min depending on dose. In conscious dogs with telemetric measurement of left ventricular pressure, dp/dt and heart rate, 2.5--30 mg/kg AR-L 115 BS orally augmented dp/dtmax by 16-92% for 5 to 12 h. Systolic blood pressure and heart rate were modestly increased. The investigation of the basal values of cardiac contractility and the efficacy of i.v. administered AR-L 115 BS in dogs pretreated with 10 mg/kg/day orally for 6 and 12 months indicated that the compound did not accumulate and that no tolerance to the drug developed.
在麻醉犬中，静脉注射0.03 - 10 mg/kg的2 - [(2 - 甲氧基 - 4 - 甲亚磺酰基)-苯基]-1H - 咪唑并[4,5 - b]吡啶（AR - L 115 BS）可使dp/dtmax增加3% - 221%，VCE增加1% - 196%。产生正性变时作用的阈剂量较高，从0.3 mg/kg开始，在10 mg/kg时可达+70%。全身血压未受到显著影响，而所有剂量下肺动脉压均略有降低，3和10 mg/kg剂量时左心室舒张末期压力也降低。在麻醉狒狒中静脉注射0.1 - 5 mg/kg以及在小型猪中静脉注射0.1 - 10 mg/kg时观察到类似效果。对收缩性参数的作用持续时间为20至100分钟，取决于剂量。在通过遥测测量左心室压力、dp/dt和心率的清醒犬中，口服2.5 - 30 mg/kg的AR - L 115 BS可使dp/dtmax在5至12小时内增加16% - 92%。收缩压和心率适度升高。对犬心脏收缩性基础值以及在口服10 mg/kg/天、持续6个月和12个月预处理的犬中静脉注射AR - L 115 BS的疗效进行的研究表明，该化合物不会蓄积，且未产生对药物的耐受性。
