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Your search keyword '"Fenton, G."' showing total 26 results
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26 results on '"Fenton, G."'

7. ChemInform Abstract: Selective Type IV Phosphodiesterase Inhibitors as Antiasthmatic Agents. The Syntheses and Biological Activities of 3-(Cyclopentyloxy)-4- methoxybenzamides and Analogues.

Author

ASHTON, M. J., primary, COOK, D. C., additional, FENTON, G., additional, KARLSSON, J.-A., additional, PALFREYMAN, M. N., additional, RAEBURN, D., additional, RATCLIFFE, A. J., additional, SOUNESS, J. E., additional, THURAIRATNAM, S., additional, and VICKER, N., additional

Published
2010
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26. BGC20-1531, a novel, potent and selective prostanoid EP receptor antagonist: a putative new treatment for migraine headache.

Author

Maubach KA, Davis RJ, Clark DE, Fenton G, Lockey PM, Clark KL, Oxford AW, Hagan RM, Routledge C, and Coleman RA

Subjects
Adult, Aged, Animals, Carotid Artery, Common drug effects, Carotid Artery, Common physiology, Cell Line, Cerebral Arteries drug effects, Cerebral Arteries physiology, Dinoprostone pharmacology, Dogs, Dose-Response Relationship, Drug, Female, Humans, In Vitro Techniques, Male, Meningeal Arteries drug effects, Meningeal Arteries physiology, Middle Aged, Muscle, Smooth, Vascular drug effects, Muscle, Smooth, Vascular physiology, Pyridines adverse effects, Pyridines therapeutic use, Radioligand Assay, Receptors, Prostaglandin E, EP4 Subtype, Recombinant Proteins antagonists & inhibitors, Sulfonamides adverse effects, Sulfonamides therapeutic use, Vasoconstriction drug effects, Vasodilator Agents adverse effects, Vasodilator Agents therapeutic use, Young Adult, Migraine Disorders drug therapy, Pyridines pharmacology, Receptors, Prostaglandin E antagonists & inhibitors, Sulfonamides pharmacology, Vasodilator Agents pharmacology
Abstract

Background and Purpose: Prostanoid EP(4) receptor antagonists may have therapeutic utility in the treatment of migraine since EP(4) receptors have been shown to be involved in prostaglandin (PG)E(2)-induced cerebral vascular dilatation, which may be an important contributor to migraine pain. This study reports the pharmacological characterization of BGC20-1531, a novel EP(4) receptor antagonist., Experimental Approach: BGC20-1531 was characterized in radioligand binding and in vitro functional assays employing recombinant and native EP(4) receptors. Changes in canine carotid haemodynamics were used to assess the pharmacodynamic profile of BGC20-1531 in vivo., Key Results: BGC20-1531 exhibited high affinity at recombinant human EP(4) receptors expressed in cell lines (pK(B) 7.6) and native EP(4) receptors in human cerebral and meningeal artery (pK(B) 7.6-7.8) but showed no appreciable affinity at a wide range of other receptors (including other prostanoid receptors), channels, transporters and enzymes (pKi < 5). BGC20-1531 competitively antagonized PGE(2)-induced vasodilatation of human middle cerebral (pK(B) 7.8) and meningeal (pK(B) 7.6) arteries in vitro, but had no effect on responses induced by PGE(2) on coronary, pulmonary or renal arteries in vitro. BGC20-1531 (1-10 mg.kg(-1) i.v.) caused a dose-dependent antagonism of the PGE(2)-induced increase in canine carotid blood flow in vivo., Conclusions and Implications: BGC20-1531 is a potent and selective antagonist at EP(4) receptors in vitro and in vivo, with the potential to alleviate the symptoms of migraine that result from cerebral vasodilatation. BGC20-1531 is currently in clinical development for the treatment of migraine headache.

Published
2009
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