SSR126768A (4-chloro-3-[(3R)-(+)-5-chloro-1-(2,4-dimethoxybenzyl)-3-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]-N-ethyl-N-(3-pyridylmethyl)-benzamide, hydrochloride): a new selective and orally active oxytocin receptor antagonist for the prevention of preterm labor.

4-chloro-3-[(3R)-(+)-5-chloro-1-(2,4-dimethoxybenzyl)-3-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]-N-ethyl-N-(3-pyridylmethyl)benzamide, hydrochloride (SSR126768A), a new potent and selective, orally active oxytocin (OT) receptor antagonist was characterized in several biochemical and pharmacological models. In binding studies, SSR126768A showed nanomolar affinity for rat and human recombinant and native OT receptors (K(i) = 0.44 nM) and exhibited much lower affinity for V(1a), V(1b), and V(2) receptors.

Altered contractility of circular and longitudinal muscle in TNBS-inflamed guinea pig ileum.

Intestinal motility disorders are often associated with gut inflammation. We evaluated, in vitro under isometric conditions, changes in contractility of longitudinal and circular muscle layers from guinea pig ileum after 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced ileitis. TNBS treatment did not modify length-active tension relationships for both muscle layers, whereas a significant increase in passive tension was observed in the circular muscle response to stretching.

Functional evidence for NO-synthase activation by substance P through a mechanism not involving classical tachykinin receptors in guinea-pig ileum in vitro.

1. This study tested the hypothesis that a nitric oxide synthase (NOS) was activated in guinea-pig ileum in vitro in response to substance P (SP), and attempted to characterize the tachykinin receptor involved in this activation by the use of selective receptor agonists and antagonists. 2.

Intraluminal excretion of PAF, lysoPAF, and acetylhydrolase in patients with ulcerative colitis.

PAF-acether (PAF) is a phospholipid synthesized by numerous inflammatory cells. PAF can produce several pathological changes in various organs, especially in the colon. In animals PAF causes colonic ulceration and inflammation, which are similar to the anatomic lesions seen in human ulcerative colitis.

Evidence for mast cell, leukotriene and nitric oxide involvement in the regulation of the adrenoceptor number of inflamed small intestine in guinea pigs.

Changes in the populations of neurotransmitter receptors involved in the control of intestinal smooth muscle function have been associated with the altered motility of the inflamed gut. Thus, trinitrobenzenesulphonic acid (TNBS)-induced gut inflammation is accompanied by an increase in alpha- and a decrease in beta-adrenoceptor numbers in guinea pig small intestine. In the present study, we investigated the effects of anti-inflammatory compounds (cyclooxygenase inhibitor indomethacin, lipooxygenase inhibitor MK-886, nitric oxide synthase inhibitor NG-nitro-L-arginine methylester (L-NAME), mast cell stabilizer doxantrazole) on TNBS-induced adrenoceptor changes.

Inverse regulation of alpha- and beta-adrenoceptors during trinitrobenzenesulfonic acid (TNB)-induced inflammation in guinea-pig small intestine.

The hypothesis has been raised that intestinal motor disturbances induced by inflammation of the digestive tract may reflect alterations in intestinal cell-membrane receptors. This question has been addressed herein for adrenoceptors by performing [3H]prazosin, [3H]rauwolscine and [3H]DHA binding studies on guinea-pig jejunal smooth-muscle membrane preparations from both healthy controls and 3, 6, and 10 days after TNB-induced intestinal inflammation. Each of the adrenoceptor subtype-selective radioligands used bound selectively to a single saturable class of sites, with no significant (p < 0.