title: The pharmacological effect of BGC20-1531, a novel prostanoid EP4 receptor antagonist, in the prostaglandin E2 human model of headache.
abstract: Using a human Prostaglandin E(2) (PGE(2)) model of headache, we examined whether a novel potent and selective EP(4) receptor antagonist, BGC20-1531, may prevent headache and dilatation of the middle cerebral (MCA) and superficial temporal artery (STA). In a three-way cross-over trial, eight healthy volunteers were randomly allocated to receive 200 and 400 mg BGC20-1531 and placebo, followed by a 25-min infusion of PGE(2). We recorded headache intensity on a verbal rating scale, MCA blood flow velocity and STA diameter. There was no difference in headache response or prevention of the dilation of the MCA or the STA (P > 0.05) with either dose of BGC20-1531 relative to placebo, although putative therapeutic exposures were not reached in all volunteers. In conclusion, these data suggest that the other EP receptors may be involved in PGE(2) induced headache and dilatation in normal subjects.
authors.affiliation: Danish Headache Center and Department of Neurology, Faculty of Health Sciences, Glostrup Hospital, University of Copenhagen, Ndr. Ringvej 67, Glostrup, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Antonova
authors.forename: Troels
authors.initials: T
authors.lastname: Wienecke
authors.forename: Karen
authors.initials: K
authors.lastname: Maubach
authors.forename: Emma
authors.initials: E
authors.lastname: Thomas
authors.forename: Jes
authors.initials: J
authors.lastname: Olesen
authors.forename: Messoud
authors.initials: M
authors.lastname: Ashina
mesh_terms: D000328:Adult; D000700:Analgesics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D018592:Cross-Over Studies; D015232:Dinoprostone / Q000633:toxicity; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D008297:Male; D011725:Pyridines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects; D055815:Young Adult; D000096926:Benzenesulfonamides
chemical_list: D000700:Analgesics; D015232:Dinoprostone; D011725:Pyridines; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013449:Sulfonamides; C541956:N-(4-(4-(5-methoxypyridin-2-yl)phenoxymethyl)-5-methylfuran-2-carbonyl)-2-methylbenzenesulfonamide; D000096926:Benzenesulfonamides