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Review ArticleReview Article

Recent Progress in Prostaglandin F2α Ethanolamide (Prostamide F2α) Research and Therapeutics

D. F. Woodward, J. W. Wang and N. J. Poloso
Eliot H. Ohlstein, ASSOCIATE EDITOR
Pharmacological Reviews October 2013, 65 (4) 1135-1147; DOI: https://doi.org/10.1124/pr.112.007088
D. F. Woodward
Department of Biological Sciences, Allergan Inc., Irvine, California
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J. W. Wang
Department of Biological Sciences, Allergan Inc., Irvine, California
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N. J. Poloso
Department of Biological Sciences, Allergan Inc., Irvine, California
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Eliot H. Ohlstein
Department of Biological Sciences, Allergan Inc., Irvine, California
Roles: ASSOCIATE EDITOR
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Abstract

Prostamide (prostaglandin ethanolamide) research emerged from two distinct lines of research: 1) the unique pharmacology of the antiglaucoma drug bimatoprost and 2) the discovery that endocannabinoid anandamide was converted by COX-2 to a series of electrochemically neutral prostaglandin (PG) ethanolamides. Bimatoprost pharmacology was found to be virtually identical to that of prostamide F2α. The earliest studies relied on comparison of agonist potencies compared with PGF2α and synthetic prostaglandin F2α (FP) receptor agonists. The subsequent discovery of selective and potent prostamide receptor antagonists (AGN 211334-6, as shown in Fig. 3) was critical for distinguishing between prostamide and FP receptor-mediated effects. The prostamide F2α receptor was then modeled by cotransfecting the wild-type FP receptor with an mRNA splicing variant (altFP4).Bimatoprost is now used therapeutically for treating both glaucoma and eyelash hypotrichosis. Bimatoprost also stimulates hair growth in isolated human scalp hair follicles. A strong effect is also seen in mouse pelage hair, where bimatoprost essentially halves the onset of hair regrowth and the time to achieve full hair regrowth in shaved mice. Beyond glaucoma and hair growth, bimatoprost has potential for reducing fat deposition. Studies to date suggest that preadipocytes are the cellular target for bimatoprost. The discovery of the enzyme prostamide/PGF synthase was invaluable in elucidating the anatomic distribution of prostamide F2α. High expression in the central nervous system provided the impetus for later studies that described prostamide F2α as a nociceptive mediator in the spinal cord. At the translational level, bimatoprost has already provided therapeutics in two distinct areas and the use of both prostamide agonists and antagonists may provide other useful medicaments.

Footnotes

  • dx.doi.org/10.1124/pr.112.007088.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 65 (4)
Pharmacological Reviews
Vol. 65, Issue 4
1 Oct 2013
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Review ArticleReview Article

Prostamide F2α Research

D. F. Woodward, J. W. Wang and N. J. Poloso
Pharmacological Reviews October 1, 2013, 65 (4) 1135-1147; DOI: https://doi.org/10.1124/pr.112.007088

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Review ArticleReview Article

Prostamide F2α Research

D. F. Woodward, J. W. Wang and N. J. Poloso
Pharmacological Reviews October 1, 2013, 65 (4) 1135-1147; DOI: https://doi.org/10.1124/pr.112.007088
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    • Abstract
    • I. Introduction
    • II. Biosynthesis of Prostamide F2α
    • III. Prostamide F2α/Bimatoprost Pharmacology
    • IV. Biologic Functions/Therapeutics
    • V. Summary and Conclusions
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