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Hexamethonium‐Type Allosteric Modulators of the Muscarinic Receptors Bearing Lateral Dibenzazepine Moieties
Author(s) -
Li Ruanto,
Tränkle Christian,
Mohr Klaus,
Holzgrabe Ulrike
Publication year - 2001
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/1521-4184(200104)334:4<121::aid-ardp121>3.0.co;2-t
Subject(s) - allosteric regulation , chemistry , stereochemistry , muscarinic acetylcholine receptor m2 , hexamethonium , muscarinic acetylcholine receptor , receptor , tricyclic , biochemistry
Alkane‐bisammonium compounds carrying lateral phthalimido substituents are known to have a high affinity for the allosteric binding site of the acetylcholine M 2 receptor. The purpose of this study was to replace the lateral phthalimido moieties with rigid tricyclic skeletons of a large volume in order to learn more about the function of the lateral heterocycles. In addition, methyl groups were introduced into the lateral connecting chains. Allosteric inhibition of the dissociation of [ 3 H]N‐methylscopolamine from the M 2 receptors in porcine cardiac homogenates served to indicate binding of the test compounds to the allosteric site. The phthalimido groups could be replaced with dibenzazepine moieties without any loss in potency. Interestingly, the additional methyl group in the lateral spacer seems to have a significant influence on the allosteric behaviour.