Abstract
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.
Footnotes
- Received September 25, 1973.
- Accepted May 21, 1974.
- © 1974 by The Williams & Wilkins Co.
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