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.
Alabaster
V A
VA
Pfizer Central Research, Kent UK.
Keir
R F
RF
Parry
M J
MJ
de Souza
R N
RN
D000818:Animals; D001773:Blood Cells / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D004095:Dihydropyridines; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D004095:Dihydropyridines; D007093:Imidazoles; D010972:Platelet Activating Factor; D011725:Pyridines; C073027:modipafant