Pendleton R G, Kaiser C, Gessner G
J Pharmacol Exp Ther. 1976 Jun;197(3):623-32.
SK&F 64139 is a potent, reversible inhibitor of phenylethanolamine N-methyltransferase; its IC50 concentration in our standard assay system was 1 X 10(-7) M. Kinetically, the compound is a competitive inhibitor with respect to norepinephrine but is uncompetitive when S-adenosylmethionine is the variable substrate. In contrast to a previously reported compound (SK&F 7698), the drug is only a weak alpha receptor antagonist (KB = 6 X 10(-6) M). In both the rat and squirrel monkey, SK&F 64139 produced dose-dependent decreases in the adrenal epinephrine content coupled with stoichiometrically equivalent increases in the norepinephrine pool(s). Further evidence for in vivo phenylethanolamine N-methyltransferase inhibitory activity was that the drug markedly inhibited the conversion of a tracer dose of 3H-norepinephrine to 3H-epinephrine in the rat adrenal gland after unit oral doses as low as 5 mg/kg.
SK&F 64139是一种强效、可逆的苯乙醇胺N-甲基转移酶抑制剂；在我们的标准检测系统中，其IC50浓度为1×10⁻⁷ M。从动力学角度来看，该化合物对去甲肾上腺素而言是竞争性抑制剂，但当S-腺苷甲硫氨酸作为可变底物时则是非竞争性抑制剂。与先前报道的一种化合物（SK&F 7698）不同，该药物只是一种弱α受体拮抗剂（KB = 6×10⁻⁶ M）。在大鼠和松鼠猴体内，SK&F 64139均使肾上腺肾上腺素含量呈剂量依赖性降低，同时去甲肾上腺素池出现化学计量学上相当的增加。体内苯乙醇胺N-甲基转移酶抑制活性的进一步证据是，该药物在大鼠肾上腺中，单位口服剂量低至5 mg/kg时，能显著抑制微量3H-去甲肾上腺素向3H-肾上腺素的转化。
