Published Online
on October 7, 2004

A more recent version of this article appeared on November 1, 2004

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Submitted on June 2, 2004
Accepted on June 2, 2004

Estrogen-Like Compounds for Ischemic Neuroprotection

James W. Simpkins PhD^*; Shao-Hua Yang MD, PhD; Ran Liu MD; Evelyn Perez PhD; Zu Yun Cai PhD; Douglas F. Covey PhD; and Pattie S. Green PhD

From the Department of Pharmacology & Neuroscience (J.W.S., S.-H.Y., R.L., E.P.), University of North Texas Health Science Center, Fort Worth, Texas; the Department of Molecular Biology and Pharmacology (Z.Y.C., D.F.C.), Washington University School of Medicine, St. Louis, Mo; and the Department of Gerontology and Geriatric Medicine (P.S.G.), School of Medicine, University of Washington, Seattle, Wash.

^* To whom correspondence should be addressed. E-mail: jsimpkin{at}hsc.unt.edu.

Abstract--We have synthesized a library of estrogen analogues, including enantiomers of estradiol and A-ring substituted estrogens. These compounds have reduced or no binding to either estrogen receptor- or estrogen receptor-, exhibit enhanced neuroprotective activity in in vitro models, and are potent in protecting brain tissue from cerebral ischemia/reperfusion injury. These potent, nonfeminizing estrogen analogues are prime candidates for use in stroke neuroprotection.

Key words: estrogens • estrogen receptors • neuroprotection • stroke