SELECTIVE BLOCKADE OF ADRENOCEPTIVE BETA RECEPTORS IN HEART
SELECTIVE BLOCKADE OF ADRENOCEPTIVE BETA RECEPTORS IN HEART
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DOI：
10.1111/j.1476-5381.1968.tb00444.x
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发表时间：
1968-01-01
影响因子：
7.3
通讯作者：
SHANKS, RG
中科院分区：
文献类型：
--
作者：
DUNLOP, D;SHANKS, RG
国际刑事法庭50172 [4-（2-hydroxy-3-isopropylaminopropoxy）acetinilide]可降低或消除麻醉犬中肾上腺素、异丙肾上腺素和去甲肾上腺素引起的心率和心脏收缩力的增加，但不影响异丙肾上腺素引起的动脉舒张压的下降。注射I.C.I. 50172注入髂外动脉并不减少动脉内注射异丙肾上腺素引起的狗后肢血流的增加。在麻醉猫中，I.C.I.可降低静脉输注异丙肾上腺素和刺激右星状神经节引起的心率增加。50172.国际刑事法庭50172具有一些拟交感神经活性，因为它增加正常猫和经西罗辛戈平预处理的猫的心率。I.C.I. 50172对异丙肾上腺素的拮抗作用比普萘洛尔和MJ 1999 [4-（2-异丙基氨基-1-羟乙基）甲磺酰苯胺盐酸盐]的拮抗作用要平缓。国际刑事法庭50172的活性为普萘洛尔的1/3 ~ 1/4。国际刑事法庭50172对肾上腺素引起的豚鼠离体气管链松弛的拮抗作用约为普萘洛尔的1/150。I.C.I.的口服和静脉给药。50172在清醒的狗中产生的异丙肾上腺素心动过速的减少比在麻醉的狗中小得多。在清醒的狗中，I.C.I. 50172在服用培吡定后升高。在清醒的狗中，异丙肾上腺素引起的心率增加是由于对窦房结的直接作用和对平均动脉压下降的反应性心率增加。麻醉猫和麻醉狗中哇巴因引起的心律失常不能被I.C.I.消除。50172但可防止麻醉猫在给予甲基氯仿和肾上腺素后发生心室纤维性颤动，并减少清醒狗在冠状动脉结扎后肾上腺素引起的心室异位搏动次数。国际刑事法庭50172无明显麻醉活性。
I.C.I. 50172 [4-(2-hydroxy-3-isopropylaminopropoxy)acetinilide] reduced or abolished the increases in heart rate and cardiac contractile force produced by epinephrine, isoprenaline and norepinephrine in anesthesized dogs but did not affect the fall in arterial diastolic pressure in response to isoprenaline. Theinjection of I.C.I. 50172 into the external iliac artery did not reduce the increase in flow to the hind limb of the dog produced by the intra-arterial injection of isoprenaline. In anesthetized cats, the increases in heart rate produced by the intravenous infusion of isoprenaline and by stimulation of the right stellate ganglion were reduced by I.C.I. 50172. I.C.I. 50172 possessed some sympathomimetic activity because it increased heart rate in normal and in syrosingopine pre-treated cats. The dose-response curves for I.C.I. 50172 for antagonism of the effects of isoprenaline in anesthetized dogs were flatter than those for propranolol and MJ 1999 [4-(2-isopropylamino-l-hy-droxyethyl) methane sulfonanilide HCl]. I.C.I. 50172 had 1/3 to 1/4 activity of propranolol. I.C.I. 50172 was about 1/150 as active as propranolol in antagonizing epinephrine-induced relaxation of isolated guinea pig tra-cheal chains. Oral and intravenous administration of I.C.I. 50172 produced a much smaller reduction in an isoprenaline tachycardia in conscious dogs than in anesthetized dogs. In conscious dogs the blocking effect of I.C.I. 50172 was increased after the administration of pempi-dine. In conscious dogs the increase in heart rate produced by isoprenaline resulted from a direct action on the sino-atrial node and from a reflex increase in heart rate in response to the fall in mean arterial pressure. Arrhythmias produced by ouabain in anesthetized cats and anesthetized dogs were not abolished by I.C.I. 50172 but is prevented the development of ventricular fibrillation in anesthetized cats on the administration of methyl chloroform and epinephrine and reduced the number of ventricular ectopic beats produced by epinephrine in conscious dogs following coronary artery ligation. I.C.I. 50172 had no logal anesthetic activity.