Rt. Li et al., Hexamethonium-type allosteric modulators of the muscarinic receptors bearing lateral dibenzazepine moieties, ARCH PHARM, 334(4), 2001, pp. 121-124
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.