Sulphasalazine analogue Ph CH 44A: Powerful and selective inhibitor of prostaglandin breakdown in vitro and in vivo

Abstract

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 μM (7 organs from 2 species) and ID 50 values of 1.6 μM and 5.0 μM 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 μM inhibited prostaglandin F 2α metabolism by 57.9±5.9%. Intravenous infusion of 3.3 μg/kg/min homosulphasalazine in the anaesthetised rat inhibited pulmonary inactivation of intravenous prostaglandin E 1 by 33.3% but did not affect the vasodepressor responses to the prostaglandin when administered intra-arterially.