Abstract
The interaction of Otilonium bromide (OB) with binding sites for 63 different receptors and ion channels in appropriate preparations has been investigated. Experiments were also performed in rat colon, the preferred tissue for OB `in vivo' uptake after oral administration.Among the receptors investigated OB binds with subμmaffinity to muscarinic M1, M2, M4, M5and PAF receptors and with μmaffinity to the diltiazem binding site on L type Ca2+channels. In the rat colon OB shows competitive interaction with the verapamil binding site on L type Ca2+channels and with muscarinic M2receptors with IC50of 1020 and 1220 nm, respectively. These findings provide a molecular rationale to explain the spasmolytic action exerted by OB on intestinal smooth muscle. In particular, a combination of antimuscarinic and Ca2+channel blocker properties seems to best account for the action of this compound.
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