Sarges R, Constantine J W, McShane W K
J Pharmacol Exp Ther. 1975 Feb;192(2):351-64.
Certain members of a series of 1-aminotetraline derivatives reversed the epinephrine pressor response in dogs; this effect occurred with the R- but not the S-isomers. Studies with rabbit aortic strips indicated competitive blockade of the alpha adrenergic receptor by the active agents. Receptor protection experiments supported the interpretation that this disruption of receptor function was due to occupancy blockade. This led to a hypothesis defining the steric properties of the alpha receptor and the active conformation of epinephrine at this receptor. However, two hydroxy substituted 1-aminotetralines ans two trihydroxytetrahydrosioquinoline derivatives, which were investigated to support this hypothesis, failed to show the predicted alpha adrenergic agonist activity. It is concluded that the interaction of certain 1-aminotetralines with a stereospecific binding site at the alpha receptor mimics occupancy blockade. However, this binding site is probably not entirely identical with the epinephrine binding site at the alpha receptor. Furthermore, the cyclic tetrahydroisoquinoline derivatives do not represent the active conformation of epinephrine at the receptor.
一系列1-氨基四氢萘衍生物中的某些成员可逆转犬体内的肾上腺素升压反应；这种效应只在R-异构体中出现，而S-异构体则不会。对兔主动脉条的研究表明，活性药物对α肾上腺素能受体具有竞争性阻断作用。受体保护实验支持了这样一种解释，即受体功能的这种破坏是由于占据性阻断所致。这导致了一个假说，该假说定义了α受体的空间特性以及肾上腺素在该受体上的活性构象。然而，为支持这一假说而研究的两种羟基取代的1-氨基四氢萘和两种三羟基四氢异喹啉衍生物，均未表现出预期的α肾上腺素能激动剂活性。得出的结论是，某些1-氨基四氢萘与α受体上的立体特异性结合位点的相互作用模拟了占据性阻断。然而，这个结合位点可能并不完全等同于α受体上的肾上腺素结合位点。此外，环状四氢异喹啉衍生物并不代表肾上腺素在受体上的活性构象。
