Studies using isolated uterine and other preparations show bimatoprost and prostanoid FP agonists have different activity profiles

June Chen, Judith Senior, Kay Marshall, Farhat Abbas, Helen Dinh, Tim Dinh, Larry Wheeler, David Woodward

    Research output: Contribution to journalArticlepeer-review


    The pharmacology of bimatoprost, a synthetic prostaglandin-amide, was examined in prostaglandin F 2α. (PGF 2α)- sensitive preparations. Bimatoprost potently contracted the rabbit isolated uterus (pEC 50 = 7.92 + 0.16). In contrast, bimatoprost exhibited weak excitatory activity in human myometrium from pregnant and nonpregnant donors, mouse uterus, rat uterus, and endothelium-intact rabbit jugular veins, and did not stimulate DNA synthesis in mouse fibroblasts. The possibility that the effects of bimatoprost may reflect partial agonism at prostanoid FP receptors was examined and the contractile effects of full agonists, 17-phenyl PGF 2α (FP) and U-46619 (TP, a control), were determined in the absence and presence of 1μM bimatoprost on the mouse uterus. Analyses of the agonist-agonist functional studies showed no antagonism, indicating that bimatoprost is not a partial agonist. Bioassay metabolism studies of bimatoprost and latanoprost (FP receptor agonist prodrug) in the rabbit uterus were conducted using recipient mouse uterus. Results indicated that the potent responses to bimatoprost in the rabbit uterus are produced by the intact molecule and not by its putative free acid metabolite, 17-phenyl PGF 2α. Some hydrolysis of latanoprost to latanoprost free acid appears to have occurred in the rabbit uterus, according to biological detection. The pharmacology of bimatoprost could not be explained by its interaction with known prostanoid FP receptors and was independent of species-, tissue-, or preparation-related factors. The potent contractile effects of bimatoprost in the rabbit uterus provide further pharmacological evidence for the presence of a novel receptor population that preferentially recognises bimatoprost. © 2005 Nature Publishing Group All rights reserved.
    Original languageEnglish
    Pages (from-to)493-501
    Number of pages8
    JournalBritish Journal of Pharmacology
    Issue number4
    Publication statusPublished - Feb 2005


    • Bimatoprost (AGN 192024)
    • DNA synthesis
    • FP receptor; rabbit; mouse; rat; human
    • Jugular vein
    • Prostaglandin F 2α (PGF 2α)
    • Uterus


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