Prostaglandin D2 (PGD2) is the major eicosanoid product of mast cells and is released in large quantities during allergic and asthmatic anaphylaxis. Two seven-transmembrane G protein-coupled receptors for PGD2, designated DP1 and CRTH2/DP2, have been identified. Activation of the DP1 receptor leads to an increase of intracellular cAMP levels. However, activation of DP2 results in mobilization of intracellular Ca2+ and an apparent decrease in intracellular cAMP. MK 0524 is a potent, selective DP1 receptor antagonist with Ki values of 0.57 nM and 0.75 µM for the DP1 and DP2 receptors, respectively.4 It inhibits PGD2-induced accumulation of cAMP in both washed platelets and platelet-rich plasma with IC50 values of 0.09 and 4.0 nM, respectively. In a sheep model of allergic rhinitis, 0.1 mg/kg MK 0524 completely blocked PGD2-induced nasal congestion. At a dose of 4 mg/kg, MK 0524 suppressed a nicotinic acid-induced vasodilatory response by 80% in a mouse model of flushing, an undesirable side-effect of niacin treatment for dyslipidemia.

AH 6809

Bimatoprost

Misoprostol

MK-2894

OC000459

ONO-AE3-208

BW 245C

BW 246C

BW A868C

CAY10471

MK 571