UK-74,505, a novel and selective PAF antagonist, exhibits potent and long lasting activity in vivo.

UK-74,505, a potent and selective PAF antagonist in vitro, has been shown to be extremely active given orally or intravenously to various species. In anaesthetised guinea pigs UK-74,505 at 30 & 100 micrograms/kg i.v. inhibited bronchoconstrictor responses to aerosolised PAF without affecting blood pressure or heart rate. The increased cutaneous vascular permeability to intradermal PAF in rats was inhibited by UK-74,505 with an ED50 of 280 +/- 5 micrograms/kg p.o. In conscious dogs, complete inhibition of PAF-induced whole blood aggregation ex-vivo occurred for at least 14 hours after an oral dose of 75 micrograms/kg. It is concluded that UK-74,505 is an effective, orally active PAF antagonist of long duration with the potential for once daily dosing.