Pharmacological and cardiovascular properties of a hydantoin derivative, BW 245 C, with high affinity and selectivity for PGD2 receptors.
Initial experiments demonstrated that the hydantoin prostaglandin derivative, BW 245 C, has potent anti-aggregatory activity on human platelets which may result from its structural similarity with one of the natural prostaglandins. The aim of the present study was to extend this preliminary pharmacological characterization and to determine which, if any, prostaglandin receptor-type is responsible for mediating the biological activity of BW 245 C. A marked species variation was observed in the anti-aggregatory potency of BW 245 C such that in the human (0.36 X PGE1) it was about one hundred times more effective than in the rat (0.003 X PGE1). The relative potencies of PGI2 (ca. 10 X PGE1) and PGE1 were, however, similar in both species. An intravenous bolus injection of 250 micrograms/kg BW 245 C lowered systolic (-23%) and diastolic (-34%) blood pressure in spontaneously hypertensive rats. In radioligand binding studies it showed a high affinity and selectivity for PGD2 platelet receptors, binding to PGI2 or PGE2 receptors was not detectable. Therefore it is concluded that the platelet and cardiovascular actions of BW 245 C are mediated by PGD2 receptors and this accounts for the observed species variation which is a characteristic of this prostaglandin.
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002417:Cattle; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006827:Hydantoins / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013931:Thromboxanes / Q000096:biosynthesis; D014599:Uterus / Q000378:metabolism
D006827:Hydantoins; D011457:Prostaglandins D; D011956:Receptors, Cell Surface; D011982:Receptors, Prostaglandin; D013931:Thromboxanes; C030669:BW 245C; D015230:Prostaglandin D2