3-甲氧基异丙肾上腺素的β-肾上腺素能受体拮抗活性。

Beta-adrenoceptor antagonist activity of 3-methoxyisoprenaline.

Bassett J R

Br J Pharmacol. 1971 Jan;41(1):113-21. doi: 10.1111/j.1476-5381.1971.tb09941.x.

Abstract

The beta-adrenoceptor antagonist activity of 3-methoxyisoprenaline, the O-methylated metabolite of isoprenaline, was studied on isolated driven atrial strip and tracheal chain preparations of the guinea-pig and on the hind limb blood flow of the dog.2. On both the atrial strip and tracheal chain preparations the blockade of responses to isoprenaline fulfilled the criteria for simple competitive inhibition.3. 3-Methoxyisoprenaline decreased the vasodilator response to isoprenaline in the dog hind limb, but did not affect the response to noradrenaline.4. 3-Methoxyisoprenaline had about 1/3,700 of the potency of propranolol as a beta-adrenoceptor antagonist on the tracheal chain preparation, 1/1,000 on the atrial strip preparation and less than 1/400 on the hind limb blood flow.5. The antagonist activity of 3-methoxyisoprenaline showed a slight specificity for cardiac beta-adrenoceptors, being 4.3 times more active on guinea-pig atria than on trachea.6. Although 3-methoxyisoprenaline antagonized the actions of isoprenaline in the three preparations, its activity was extremely weak. It is unlikely that the formation of 3-methoxyisoprenaline from isoprenaline, administered therapeutically, could lead to beta-adrenoceptor blockade.

摘要

对异丙肾上腺素的O-甲基化代谢产物3-甲氧基异丙肾上腺素的β-肾上腺素受体拮抗活性进行了研究，实验对象为豚鼠的离体起搏心房条和气管链标本以及犬的后肢血流。
在心房条和气管链标本上，对异丙肾上腺素反应的阻断均符合简单竞争性抑制的标准。
3-甲氧基异丙肾上腺素可降低犬后肢对异丙肾上腺素的血管舒张反应，但不影响对去甲肾上腺素的反应。
在气管链标本上，3-甲氧基异丙肾上腺素作为β-肾上腺素受体拮抗剂的效价约为普萘洛尔的1/3700，在心房条标本上为1/1000，在后肢血流实验中则小于1/400。
3-甲氧基异丙肾上腺素的拮抗活性对心脏β-肾上腺素受体表现出轻微的特异性，对豚鼠心房的活性比对气管的活性高4.3倍。
尽管3-甲氧基异丙肾上腺素在这三种标本中均能拮抗异丙肾上腺素的作用，但其活性极弱。治疗性给予异丙肾上腺素后形成3-甲氧基异丙肾上腺素不太可能导致β-肾上腺素受体阻断。