RT Journal Article
SR Electronic
T1 THE BIOLOGICAL ACTIVITY OF THE (15S)-15-METHYL ANALOGS OF PROSTAGLANDINS E<sub>2</sub> AND F<sub>2α</sub>
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 67
OP 74
VO 186
IS 1
A1 JAMES R. WEEKS
A1 DONALD W. DuCHARME
A1 WAYNE E. MAGEE
A1 WILLIAM L. MILLER
YR 1973
UL http://jpet.aspetjournals.org/content/186/1/67.abstract
AB The biological activity of the (15S)-15-methyl analogs of prostaglandin (PG) E2 methyl ester and PGF2α methyl ester were compared in vitro on the isolated gerbil colon and rat uterus and in vivo for their antifertility effects in the hamster and cardiovascular effects in anesthetized dogs and rats. The initial step in the metabolism of PGE2 and PGF2α is an oxidation at carbon 15 by 15-hydroxy prostaglandin dehydrogenase. These analogs are not substrates for this enzyme. 15-Methylation caused only slight changes in the activity on isolated tissues and in the magnitude and duration of the cardiovascular responses. These data are consistent with efficient means of inactivation in vivo other than 15-dehydrogenation. However, at high doses 15-methylation of PGE2 methyl ester qualitatively changed the mechanism of its depressor action in the dog. PGE2 methyl ester, at 1 and 3.2 µg/kg, lowered blood pressure by a decrease in total peripheral resistance, whereas the 15-methyl analog did so by depressing myocardial contractility and cardiac output. In striking contrast, the antifertility activity of the 15-methyl analogs was increased 50- to over 100-fold over time PGE2 and PGF2α Parent compounds, respectively. © 1972 by The Williams &amp; Wilkins Co.