Use of AHR-5850 and AHR-6293 to distinguish the effect of anti-platelet aggregating drug properties from the effect of anti-inflammatory properties on an in Vivo model of platelet aggregation

Platelet aggregates are induced in arterioles on the cerebral surface by exposing the vessels to appropriately filtered light from a mercury lamp in the presence of an intraluminal fluorescent dye acting as a target for the radiant energy. The aggregates are inhibited by intraperitoneal injection of AHR-5850, but not by AHR-6293. Both drugs are potent antiinflammatory agents, AHR-6293 being more potent than AHR-5850. Both drugs inhibit platelet aggregation in vitro, but the 6293 is a much weaker inhibitor than 5850. In view of their relative potencies as anti-inflammatory and anti-aggregating agents, it appears that it is the anti-aggregating properties of 5850 which are responsible for its effect in our in vivo model, and that potent anti-inflammatory properties alone cannot account for the inhibition of platelet aggregation which we observed. The data support our earlier hypothesis that agents like aspirin and indomethacin inhibit platelet aggregation in this model because of their effect on the platelet, rather than by any anti-inflammatory protective action on the vessel wall.