PREVENTION OF PLATELET-ACTIVATING FACTOR-INDUCED GASTROINTESTINAL LESIONS IN RATS BY THE NEW SPECIFIC ANTAGONIST HYL)[4-(2,4,6-TRIISOPROPYLPHENYL)THIAZOL-2YL]AMINE

SR 27417 (CAS 136468-36-5, )[4-(2,4,6-triisopropylphenyl)thiazol-2-yl] amine), a highly potent platelet-activating factor (PAF) receptor anta gonist, was tested for its ability to prevent macroscopic and histolog ically assessed gastrointestinal (GI) lesions in rats induced by PAF a s compared to the reference compound apafant. Both compounds were oral ly effective but SR 27417 prevented the gut lesioning effects of PAF a t lower doses than apafant. In addition, a dose of apafant (1.5 mg/kg) that showed almost maximal effect when given 30 min before PAF, had l ost most of its protective action by 3 h, while SR 27417 at a comparab ly effective dose (0.5 mg/kg) retained substantial ability to prevent gut lesions in all the GI tract segments investigated, 18 h after admi nistration. These findings suggest that SR 27417 is a potent and long lasting inhibitor of PAF-induced gastrointestinal lesions in rats.