Rossi E C, Louis G, Zeller E A
J Lab Clin Med. 1979 Feb;93(2):286-94.
PEA is a potent inhibitor (Ki approximately 13 microM) of human platelet aggregation induced by epinephrine. This led us to perform an SAR study of a congeneric series of compounds in an effort to identify the molecular components of epinephrine critical to its aggregating effect upon human platelets. Phenylethanolamine was similar to PEA in inhibitory potency. However, hydroxylation of the phenyl ring diminished the inhibitory effect (Ki tyramine approximately 87 microM; Ki octopamine approximately 88 microM). Dopamine, the weakest inhibitor (Ki approximately 150 microM), was a partial agonist capable of inducing platelet aggregation in some samples of PRP. The order of potency of catecholamines as aggregating agents was epinephrine greater than norepinephrine greater than Epinine greater than dopamine. Phenylephrine, the prototype alpha-agonist, did not induce aggregation but was a potent inhibitor (Ki approximately 12 microM) of the aggregation induced by epinephrine. Isoproterenol, the prototype beta-agonist, was neither an aggregant nor an inhibitor of epinephrine-induced platelet aggregation. These findings suggest that the binding of epinephrine to the alpha-adrenergic receptor responsible for platelet aggregation is accomplished by the N-methyl amino group whereas intrinsic aggregating activity is a function of the catechol moiety.
苯乙胺是肾上腺素诱导的人血小板聚集的强效抑制剂（抑制常数Ki约为13微摩尔）。这促使我们对一系列同类化合物进行构效关系研究，以确定肾上腺素对人血小板聚集作用至关重要的分子成分。苯乙醇胺在抑制效力上与苯乙胺相似。然而，苯环羟基化会减弱抑制作用（酪胺的Ki约为87微摩尔；章鱼胺的Ki约为88微摩尔）。多巴胺是最弱的抑制剂（Ki约为150微摩尔），在某些富血小板血浆样本中是一种能够诱导血小板聚集的部分激动剂。儿茶酚胺作为聚集剂的效力顺序为：肾上腺素＞去甲肾上腺素＞Epinine＞多巴胺。去氧肾上腺素，原型α激动剂，不诱导聚集，但对肾上腺素诱导的聚集是一种强效抑制剂（Ki约为12微摩尔）。异丙肾上腺素，原型β激动剂，既不是聚集剂也不是肾上腺素诱导的血小板聚集的抑制剂。这些发现表明，肾上腺素与负责血小板聚集的α肾上腺素能受体的结合是通过N - 甲基氨基完成的，而内在聚集活性是儿茶酚部分的功能。
