Pharmacological profile of MEN91507, a new CysLT1 receptor antagonist

Heterogeneous effect of leucotriene CysLT1 receptor antagonists on antigen‐induced motor and inflammatory responses in guinea‐pig airways

“…However in guinea‐pig liver homogenates, the in vitro metabolic stability of MEN91507 and montelukast were comparable after 1 h incubation (data not shown), suggesting that the differential activity of these two antagonists cannot be attributed to a different extent of hepatic degradation in this species. To support this hypothesis, in previous experiments, these CysLT 1 receptor antagonists, at the intravenous dose of 0.4 μ mol kg −1 , potently antagonized LTD 4 ‐induced microvascular leakage in guinea‐pig trachea, and inhibited the bronchoconstrictor response induced by exogenous administration of LTD 4 in guinea‐pigs at 5 min from either MEN91507 or montelukast administration (ED 50 : 3.0 and 7.5 nmol kg −1 i.v., respectively, Cabré et al. , 2002).…”

“…The selectivity of MEN91507 has been tested at 1 μ m concentration through binding experiments at 30 different molecular targets and no significant interactions were detected (Cabré et al. , 2002).…”

“…, 2003). Indeed in guinea‐pigs, the exogenous administration of LTD 4 induces bronchoconstriction and microvascular leakage, and both effects are blocked by selective CysLT 1 receptor antagonists (Cabré et al. , 2002).…”

“…, 1992a). MEN91507 is a novel, potent and selective CysLT 1 receptor antagonist that displays a pharmacological profile which when used on guinea‐pig in vitro and in vivo preparations is comparable with that of montelukast (Cabré et al. , 2002).…”

Trapping of a Nonpeptide Ligand by the Extracellular Domains of the Gonadotropin-Releasing Hormone Receptor Results in Insurmountable Antagonism

“…Although many insurmountable compounds with slow dissociation kinetics of the antagonist-receptor complex have been described previously (Keith et al, 1989;Cabré et al, 2002;Jakubík et al, 2002;Rashid et al, 2002), only a few of these have been studied at the molecular level (Cucchi et al, 2005;Mathiesen et al, 2006;Sullivan et al, 2006). Moreover, only the dissociation kinetics of the insurmountable antagonist candesartan from its target receptor, the angiotensin II type 1 receptor, has been investigated at the level of specific molecular interactions between the chemical moieties of the compound and the residues composing its receptor binding pocket (Takezako et al, 2004).…”