BGC20‐1531, a novel, potent and selective prostanoid EP4 receptor antagonist: a putative new treatment for migraine headache

Background and purpose: Prostanoid EP4 receptor antagonists may have therapeutic utility in the treatment of migraine since EP4 receptors have been shown to be involved in prostaglandin (PG)E2‐induced cerebral vascular dilatation, which may be an important contributor to migraine pain. This study reports the pharmacological characterization of BGC20‐1531, a novel EP4 receptor antagonist. Experimental approach: BGC20‐1531 was characterized in radioligand binding and in vitro functional assays employing recombinant and native EP4 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 EP4 receptors expressed in cell lines (pKB 7.6) and native EP4 receptors in human cerebral and meningeal artery (pKB 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