Sulphasalazine analogue Ph CH 44A: powerful and selective inhibitor of prostaglandin breakdown in vitro and in vivo.
Sulphasalazine analogue Ph CH 44A (homosulphasalazine) is a potent inhibitor of prostaglandin inactivation in cell-free 100,000 g supernatants, producing 68.7 +/- 6.0% inhibition at 2 micro M (7 organs from 2 species) and ID50 values of 1.6 micro M and 5.0 micro M in human placenta and rat colon respectively. In the latter organs it was 63 and 20 times more potent than the established prostaglandin 15-hydroxydehydrogenase inhibitor sulphasalazine. Homosulphasalazine is an even weaker inhibitor of prostaglandin synthesis than sulphasalazine, with approximately half the potency on a sheep seminal vesicle preparation. It enhanced prostaglandin synthesis in a 14,000 g supernatant from rabbit kidney medulla. In isolated perfused rat lung homosulphasalazine at 50 micro M inhibited prostaglandin F2 alpha metabolism by 57.9 +/- 5.9%. Intravenous infusion of 3.3 microgram/kg/min homosulphasalazine in the anaesthetised rat inhibited pulmonary inactivation of intravenous prostaglandin E1 by 33.3% but did not affect the vasodepressor responses to the prostaglandin when administered intra-arterially.
D000818:Animals; D002474:Cell-Free System; D003864:Depression, Chemical; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D008297:Male; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis / Q000378:metabolism*; D011460:Prostaglandins F / Q000378:metabolism; D051381:Rats; D012460:Sulfasalazine / Q000494:pharmacology / Q000031:analogs & derivatives
D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011460:Prostaglandins F; D012460:Sulfasalazine; C024308:homosulphasalazine