Abstract
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.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|