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

Abstract

1 The pharmacology of bimatoprost, a synthetic prostaglandin-amide, was examined in prostaglandin F 2a (PGF 2a )-sensitive preparations. Bimatoprost potently contracted the rabbit isolated uterus (pEC 50 ¼ 7.9270.16). In contrast, bimatoprost exhibited weak excitatory activity in human myometrium from pregnant and nonpregnant donors, mouse uterus, rat uterus, and endotheliumintact 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 PGF 2a (FP) and U-46619 (TP, a control), were determined in the absence and presence of 1 mM 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 PGF 2a . 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.

Recent Progress in Prostaglandin F2αEthanolamide (Prostamide F2α) Research and Therapeutics

“…At the pharmacological level, the earliest studies used isolated tissue preparations Matias et al, 2004;Chen et al, 2005) and suggested the existence of receptors that not only preferentially recognized prostamide F 2a but also accepted prostamides D 2 and E 2 . Later studies were performed using cells and organ culture Spada et al, 2005;Wan et al, 2007;Stamer et al, 2010), and the primary focus was bimatoprost, as a prostamide F 2a analog.…”

The role of endocannabinoids in pregnancy

“…Anandamide can also be directly converted to PGH 2 by PGHS-2 and subsequently metabolised to form PMs; only anandamide-derived PGH 2 -ethanolamine (PMH 2 ) is metabolised to PMs. Synthetic PG-amide (Bimatoprost, which activates PM-sensitive receptors) weakly elicits contractions in both pregnant and nonpregnant human isolated myometrial tissues, whereas the tissues are responsive to 17-phenylprostaglandin F 2a (Chen et al 2005). The weak contractility induced by PMs could result from their low affinity for PG receptors (Ross et al 2002).…”

Eicosanoids as Diagnostics for Preterm Labor

“…Bimatoprost, a synthetic PM which activates PM-sensitive receptors, weakly elicits contractions in both pregnant and nonpregnant human isolated myometrial tissue, whereas the tissues exhibit a stronger response to 17-phenyl-prostaglandin F 2α . 42 The weak contractions elicited by PMs could result from their low affinity for PG receptors because the affinity of PME 2 for PGE 2 receptors is at least 500-fold lower than that of PGE 2 .…”