STUDIES ON SK AND F 29661, AN ORGAN-SPECIFIC INHIBITOR OF PHENYLETHANOLAMINE N-METHYLTRANSFERASE

  • 1 January 1979
    • journal article
    • research article
    • Vol. 208  (1) , 24-30
Abstract
SK and F 29661 [7,8-dichloro-1,2,3,4-tetrahydroisoquinoline] is an effective, reversible inhibitor of both CNS and adrenal phenylethanolamine N-methyl-transferase [PNMT] in vitro; its Ki [inhibition constant] values in standard assay systems were 6 .times. 10-7 M (CNS) and 3 .times. 10-7 M (adrenal), respectively. In vivo, the drug inhibited the conversion of [3H]norepinephrine to [3H]epinephrine in the rat adrenal gland and upon chronic administration decreased the endogenous adrenal epinephrine/norepinephrine ratio in both the rat and squirrel monkey. SK and F 29661 did not, however, reduce rat brain stem PNMT activity after systemic administration; subsequent radioautographic studies indicated that the compound did not enter the CNS, presumably because of its high polarity. This drug may be useful in defining the physiological importance of peripheral PNMT inhibition.