Pendleton R G, Weiner G, Jenkins B
Res Commun Chem Pathol Pharmacol. 1977 Jun;17(2):201-13.
We have found that the potency of SK&F 64139 in inhibiting rabbit adrenal phenylethanolamine N-methyltransferase (PNMT) is a function of protein concentration when high concentrations of the latter are employed. At lower enzyme levels, however, the degree of inhibition produced by the drug becomes independent of PNMT, allowing for the proper calculation of an inhibition constant. The Ki for the compound under these circumstances was 3 nM. Inhibitor dissociation constants within the same order of magnitude were subsequently obtained using the adrenal enzyme obtained from the rat, cow, dog, human and squirrel monkey. These data provide evidence that the PNMT receptor sites for SK&F 64139 do not differ substantially from species to species and suggest the general utility of this drug as an inhibitor of adrenal epinephrine biosynthesis.
我们发现，当使用高浓度的兔肾上腺苯乙醇胺N-甲基转移酶（PNMT）时，SK&F 64139抑制该酶的效力是蛋白质浓度的函数。然而，在较低的酶水平下，该药物产生的抑制程度与PNMT无关，从而可以正确计算抑制常数。在这些情况下，该化合物的Ki为3 nM。随后，使用从大鼠、牛、狗、人类和松鼠猴获得的肾上腺酶，获得了处于相同数量级的抑制剂解离常数。这些数据证明，SK&F 64139的PNMT受体位点在不同物种之间没有实质性差异，并表明该药物作为肾上腺肾上腺素生物合成抑制剂具有普遍用途。
