Hexamethonium-type allosteric modulators of the muscarinic receptors bearing lateral dibenzazepine moieties

Alkane-bisammonium compounds carrying lateral phthalimido substituents are known to have a high affinity for the allosteric binding site of the acetyl choline M-2 receptor. The purpose of this study was to replace the lateral phthalimido moieties with rigid tricyclic skeletons of a large volume in or der to learn more about the unction of the lateral heterocycles. In additio n, methyl groups were introduced into the lateral connecting chains. Allost eric inhibition of the dissociation of [H-3]N-methylscopolamine from the :M -2 receptors in porcine cardiac homogenates served to indicate binding of t he test compounds to the allosteric site. The phthalimido groups could be r eplaced with dibenzazepine moieties without any loss in potency. Interestin gly, the additional methyl group in the lateral spacer seems to have a sign ificant influence on the allosteric behaviour.