Jun 1, 1976

Studies on adrenal phenylethanolamine N- methyltransferase (PNMT) with S K & F 64139, a selective inhibitor

The Journal of Pharmacology and Experimental Therapeutics
R G PendletonG Gessner

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.

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Mentioned in this Paper

Genus Saimiri
Antagonist Muscle Action
Norepinephrine, (+, -)-Isomer
Adrenergic alpha-Antagonists
Monoamine Oxidase
Pnmt
Glycine N-Methyltransferase Deficiency
Epinephrine Measurement
Medihaler-Epi
RIMA (Reversible Inhibitor of Monoamine Oxidase A)

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