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Effect of 17β‐estradiol and the nonsteroidal benzothiophene, LY117018 on in vitro rat aortic responses to norepinephrine, serotonin, U46619, and BAYK 8644
Author(s) -
Cohen Marlene L.,
Susemichel Alice D.
Publication year - 1996
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199602)37:2<97::aid-ddr5>3.0.co;2-g
Subject(s) - medicine , endocrinology , estrogen , agonist , calcium channel , chemistry , dihydropyridine , antagonist , estrogen receptor , benzothiophene , calcium , voltage dependent calcium channel , pharmacology , receptor , biology , organic chemistry , cancer , breast cancer , thiophene
Several nonsteroidal benzothiophene derivatives that share many of the properties of estrogen have been synthesized as potential estrogen replacement therapy in postmenopausal women. LY117018 is a prototypic benzothiophene derivative that has high binding affinity for the estradiol receptor, an affinity similar to that of estradiol. The present study was designed to compare the vascular effects of β‐estradiol to those of LY117018. Estradiol (10 −5 M) was a relatively weak inhibitor of the contractile responses to norepinephrine, serotonin, and U46619 in the rat aorta. Inhibition of the contraction to these receptor agonists by β‐estradiol was a reflection of the weak calcium channel antagonist activity of β‐estradiol as demonstrated by the inhibition of the calcium agonist‐induced contractions produced by BayK 8644. Like β‐estradiol, LY117018 (10 −6 and 10 −5 M) also inhibited the contractile responses to norepinephrine, serotonin, U46619, and BayK 8644. However, LY117018 was a more potent calcium channel antagonist in vascular tissue than β‐estradiol. Inhibition of these contractile responses by both β‐estradiol and LY117018 was independent of an intact endothelium. Since β‐estradiol and LY117018 possess similar affinity for the β‐estradiol receptor, yet have different abilities to produce calcium channel blockade in vascular tissue, it is unlikely that calcium channel blockade by these agents is related to their ability to bind to the estrogen receptor. Furthermore, to the extent that calcium channel inhibition may contribute to the beneficial clinical effects of estrogen, LY117018 may have important advantages relative to estrogen as replacement therapy in postmenopausal women. © 1996 Wiley‐Liss, Inc.