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

Studies using isolated uterine and other preparations show bimatoprost and prostanoid FP agonists... 1 The pharmacology of bimatoprost, a synthetic prostaglandin‐amide, was examined in prostaglandin F2α (PGF2α)‐sensitive preparations. Bimatoprost potently contracted the rabbit isolated uterus (pEC50=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. 2 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 PGF2α (FP) and U‐46619 (TP, a control), were determined in the absence and presence of 1 μM bimatoprost on the mouse uterus. Analyses of the agonist–agonist functional studies showed no antagonism, indicating that bimatoprost is not a partial agonist. 3 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 PGF2α. Some hydrolysis of latanoprost to latanoprost free acid appears to have occurred in the rabbit uterus, according to biological detection. 4 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. British Journal of Pharmacology (2005) 144, 493–501. doi:10.1038/sj.bjp.0706044 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

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

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Publisher
Wiley
Copyright
2005 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1038/sj.bjp.0706044
pmid
15678094
Publisher site
See Article on Publisher Site

Abstract

1 The pharmacology of bimatoprost, a synthetic prostaglandin‐amide, was examined in prostaglandin F2α (PGF2α)‐sensitive preparations. Bimatoprost potently contracted the rabbit isolated uterus (pEC50=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. 2 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 PGF2α (FP) and U‐46619 (TP, a control), were determined in the absence and presence of 1 μM bimatoprost on the mouse uterus. Analyses of the agonist–agonist functional studies showed no antagonism, indicating that bimatoprost is not a partial agonist. 3 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 PGF2α. Some hydrolysis of latanoprost to latanoprost free acid appears to have occurred in the rabbit uterus, according to biological detection. 4 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. British Journal of Pharmacology (2005) 144, 493–501. doi:10.1038/sj.bjp.0706044

Journal

British Journal of Pharmacology – Wiley

Published: Feb 1, 2005

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