Prevention of platelet-activating factor-induced gastrointestinal lesions in rats by the new specific antagonist N-(2-dimethylaminoethyl)-N-(3-pyridinylmethyl)[4-(2,4,6-triisopropylphe nyl) thiazol-2yl]amine.
SR 27417 (CAS 136468-36-5, N-(2-dimethylaminoethyl)-N-(3-pyridinylmethyl)[4-(2,4,6-triisop ropylphenyl) thiazol-2-yl]amine), a highly potent platelet-activating factor (PAF) receptor antagonist, was tested for its ability to prevent macroscopic and histologically assessed gastrointestinal (GI) lesions in rats induced by PAF as compared to the reference compound apafant. Both compounds were orally effective but SR 27417 prevented the gut lesioning effects of PAF at 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 lost most of its protective action by 3 h, while SR 27417 at a comparably effective dose (0.5 mg/kg) retained substantial ability to prevent gut lesions in all the GI tract segments investigated, 18 h after administration. These findings suggest that SR 27417 is a potent and long lasting inhibitor of PAF-induced gastrointestinal lesions in rats.
Giudice
A
A
Herbert
J M
JM
Maffrand
J P
JP
Manara
L
L
Manzoni
L
L
Le Fur
G
G
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000473:pathology; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D013844:Thiazoles / Q000627:therapeutic use*; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D013844:Thiazoles; D014230:Triazoles; C052518:WEB 2086; C071317:Foropafant