Replacement of the carboxylic acid group of prostaglandin F_2α with a hydroxyl or methoxy substituent provides biologically unique compounds

Abstract

uprostenol. In the rat uterus, PGF 2a 1-OH was about two orders of magnitude less potent than 17-phenyl PGF 2a whereas PGF 2a 1-OCH 3 produced only a minimal e ect. 4 Radioligand binding studies on cat lung parenchymal plasma membrane preparations suggested that the cat lung parenchyma does not contain a homogeneous population of receptors that equally respond to PGF 2a 1-OH, PGF 2a 1-OCH 3 , and classical FP receptor agonists. 5 Studies on smooth muscle preparations and cells containing DP, EP 1 , EP 2 , EP 3 , EP 4 , IP, and TP receptors indicated that the activity of PGF 2a 1-OH and PGF 2a 1-OCH 3 could not be ascribed to interaction with these receptors. 6 The potent e ects of PGF 2a 1-OH and PGF 2a 1-OCH 3 on the cat lung parenchyma are di cult to describe in terms of interaction with the FP or any other known prostanoid receptor.

Pharmacological Characterization of a Novel Antiglaucoma Agent, Bimatoprost (AGN 192024)

“…The pharmacology of these COX-2 products remains to be studied in detail but initial studies suggest that they are pharmacologically novel and that their activities may be unrelated to prostaglandin or cannabinoid receptor stimulation (Berglund et al, 1999;Woodward et al, 2001;Ross et al, 2002). These findings are consistent with a recent study describing the unique pharmacology of synthetic structural analogs of prostaglandin (PG) F 2␣ , where the carboxylic acid group has been replaced by a nonionizable hydroxy or methoxy substituent (Woodward et al, 2000).…”

“…The functional and radioligand binding methods for the cat lung parenchyma are as described previously (Woodward et al, 2000). The cat lung parenchymal strip was used in conjunction with additional isolated tissue preparations to assist in characterizing the pharmacology of bimatoprost.…”

“…In addition to in vitro pharmacological characterization of bimatoprost, its effects on intraocular pressure and its metabolic fate in living nonhuman primate eyes are described. This is important because it determines whether effects on intraocular pressure result from its inherent pharmacological activity or occur, at least in part, by virtue of enzymatic hydrolysis to a free acid metabolite that would behave as an authentic prostanoid FP receptor agonist (Woodward and Lawrence, 1994;Woodward et al, 2000). Thus, particular attention is devoted to studying potential 17-phenyl PGF 2␣ formation in ocular tissues and pharmacological comparisons are made directly to 17-phenyl PGF 2␣ .…”

Synergistic antinociceptive effects of anandamide, an endocannabinoid, and nonsteroidal anti-inflammatory drugs in peripheral tissue: A role for endogenous fatty-acid ethanolamides?

“…A reason could be the local pH values of the tested substances, however, the pH of ibuprofen and rofecoxib were found to be similar and not different from normal saline (data not shown). Finally, it could be that in the presence of a COX-2 inhibitor, less anandamide can be converted into its COX-2 metabolite, PGF 2α ethanolamide (Woodward et al, 2000).…”

Formation of prostamides from anandamide in FAAH knockout mice analyzed by HPLC with tandem mass spectrometry

“…COX-2 may be a potential key enzyme in anandamide conversion to prostamides (prostanoid ethanolamides) in vivo. These prostamides possess biological activity (13,14), including contraction of feline cat iris and the reduction of intraocular pressure in primates. Furthermore, these prostamides have longer plasma elimination half-life when compared with prostaglandins (15).…”