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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Polymethylene tetraamines as muscarinic receptor probes.

The possibility that polymethylene tetraamines act as divalent ligands has been explored. Structure-activity relationship studies among polymethylene tetraamines have shown that four nitrogens are necessary for high affinity binding to M2 receptors while being less important for M3 muscarinic receptors. Replacement of one terminal methoxybenzyl group of the potent and selective muscarinic antagonist methoctramine by different moieties led to weaker antagonists suggesting that the two terminal nitrogens of methoctramine interact with two similar receptor sites. Data are presented which suggest that methoctramine might interact with four acidic residues of the receptor: two residues are buried in the third transmembrane segment whereas the others are located extracellularly on the loop 4-5 which may represent the allosteric site where several antagonists such as gallamine bind. An hypothetical model describing the interaction of methoctramine with the M2 receptor is proposed. It may provide a useful working hypothesis for the design of new selective muscarinic ligands.[1]


  1. Polymethylene tetraamines as muscarinic receptor probes. Melchiorre, C., Minarini, A., Angeli, P., Giardinà, D., Gulini, U., Quaglia, W. Trends Pharmacol. Sci. (1989) [Pubmed]
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