RT Journal Article
SR Electronic
T1 STUDIES ON SK&F 7698; AN INHIBITOR OF PHENYLETHANOLAMINE N-METHYLTRANSFERASE (PNMT)
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 551
OP 562
VO 190
IS 3
A1 Robert G. Pendleton
A1 Carl Kaiser
A1 George Gessner
A1 Elizabeth Finlay
A1 Harry Green
YR 1974
UL http://jpet.aspetjournals.org/content/190/3/551.abstract
AB 3-Methyl-1,2,3,4-tetrahydro[1]benzothieno[3,2-c] pyridine hydrochloride (SK&F 7698) is a potent in vitro inhibitor of phenylethanolamine N-methyltransferase (PNMT) : its 150 in a standard assay was 7 x 10-7 M. The compound is a competitive inhibitor of the enzyme with respect to norepinephrine (NE) but is uncompetitive when S-adenosylmethionine is the variable substrate. In the rat, the compound selectively reduced the adrenal content of epinephrine (E) upon chronic oral administration. The adrenal NE levels were not decreased and no changes were produced in the heart and brain catecholamine content. Further evidence for in vivo PNMT inhibiting activity was the fact that the degree of conversion of a tracer dose of 3H-NE to 3H-E in the adrenal gland was inhibited by drug pretreatment. SK&F 7698 also produced alpha adrenergic blocking effects both in vitro and in vivo at doses approximating those required to inhibit PNMT and increased the rate of urinary excretion of both E and NE. © 1974 by The Williams & Wilkins Co.