ABSTRACT
The purpose of producing Platelet-activating factor (PAF) antagonists is two-fold: first, PAF antagonists are needed in the study of PAFs mode of action and, second, they are potentially useful as drugs in the treatment of diseases in which PAF takes part. The measurement of platelet aggregation is a simple procedure and well suited for the primary screening of PAF antagonists. GS 1065-180 was the first of the more potent PAF antagonists synthesized at Leo this compound was taken through further evaluation in pharmacological test. PAF is recognized as a mediator in inflammatory disorders. In order to investigate the potential of PAF antagonists in inflammatory diseases GS 1065-180 was tested in the carrageenin induced rat paw edema. GS 1065180 was ineffective to inhibit ovalbumin provoked passive cutaneous anaphylaxis or acute carrageenin edema in the rat. However, PAF-induced gastric damage was reduced by GS 1065-180, dosed intravenously.
