THE PHARMACOLOGY OF A BETA-2-SELECTIVE ADRENOCEPTOR ANTAGONIST (ICI-118,551)
THE PHARMACOLOGY OF A BETA-2-SELECTIVE ADRENOCEPTOR ANTAGONIST (ICI-118,551)
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DOI：
10.1097/00005344-198305000-00013
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发表时间：
1983-01-01
影响因子：
3
通讯作者：
WALE, JL
中科院分区：
文献类型：
--
作者：
BILSKI, AJ;HALLIDAY, SE;WALE, JL
虽然[β]1-肾上腺素受体的特定拮抗剂，如阿替洛尔和倍他洛尔，已经广泛可用，但对[β]2-肾上腺素受体具有选择性的有效的特异性拮抗剂尚未得到描述。先前描述的2-选择性拮抗剂，如丁毒胺、H 35/25和IPS 339缺乏效力、特异性或适当的2-选择性。ICI 118,551[erythro-dl-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol]对[β]2-肾上腺素能受体具有高度的选择性和特异性。通过比较心得安和ICI118,551对豚鼠心房和子宫的拮抗力(以PA2值表示)和异丙肾上腺素的作用，确定了它们对[β]受体的亲和力。ICI 118,551对子宫[β]2受体的亲和力高于心得安(分别为9.26和8.64)，而对心房[β]1受体的亲和力较低(分别为7.17和8.30)。因此，ICI118、551和心得安的体外[β]2/[β]1选择性比分别为123、551和2.2。比较了ICI118、551和阿替洛尔对异丙肾上腺素的变时性和血管扩张作用的效力和选择性。ICI118、551和阿替洛尔在血管[β]-肾上腺素受体上的表观K‘B值分别为2.1、551和253[mU]g/kg，拮抗异丙肾上腺素的血管和心房作用的效价比为>；250：1。就辅助药理性质而言，ICI118、551没有部分激动剂活性，但具有与心得安相似的膜稳定作用。
While specific antagonists of the [beta] 1-adrenoceptor, such as atenolol and betaxolol, are widely available, a potent specific antagonist selective for the [beta] 2-adrenoceptor has yet to be described. Previously described [beta] 2-selective antagonists such as butoxamine, H 35/25, and IPS 339 are lacking in potency, specificity, or appropriate [beta] 2-selectivity. ICI 118,551 [erythro-dl-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol] possesses a high degree of selectivity and specificity for the [beta] 2-adrenoceptor. The affinity of propranolol and ICI 118,551 for [beta]-adrenoceptors has been determined by comparing their antagonist potencies, expressed as pA2 values, against the actions of isoproterenol on the guinea pig atrium and uterus. ICI 118,551 had a higher affinity for the uterine [beta] 2-receptor than did propranolol (pA2 9.26 and 8.64, respectively) but a lower affinity for the atrial [beta] 1-receptor (pA2 7.17 and 8.30, respectively). Thus, the [beta] 2/[beta] 1-selectivity ratios, in vitro, were 123 for ICI 118,551 and 2.2 for propranolol. The potency and selectivity of ICI 118,551 and atenolol on the chronotropic and vasodilator actions of isoproterenol were compared in anaesthetised dogs. The apparent K'B values at the vascular [beta]-adrenoceptor were 2.1 [mu] g/kg for ICI 118,551 and 253 [mu] g/kg for atenolol, and the potency ratio for antagonism of vascular versus atrial actions of isoproterenol was> 250: 1. In regard to ancillary pharmacological properties, ICI 118,551 has no partial agonist activity but has a membrane-stabilising action similar to that of propranolol.