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  • Title: The effect of phenylethanolamine n-methyltransferase concentration and species difference on the inhibitory potency of SK&F 64139.
    Author: Pendleton RG, Weiner G, Jenkins B.
    Journal: Res Commun Chem Pathol Pharmacol; 1977 Jun; 17(2):201-13. PubMed ID: 406652.
    Abstract:
    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.
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