Back to Search
Start Over
Carbachol dimers as homobivalent modulators of muscarinic receptors.
- Source :
-
Biochemical Pharmacology . May2016, Vol. 108, p90-101. 12p. - Publication Year :
- 2016
-
Abstract
- A series of homodimers of the well-known cholinergic agonist carbachol have been synthesized, showing the two agonist units symmetrically connected through a methylene chain of variable length. The new compounds have been tested on the five cloned muscarinic receptors (hM 1–5 ) expressed in CHO cells by means of equilibrium binding studies, showing an increase in affinity by rising the number of methylene units up to 7 and 9. Functional experiments on guinea-pig ileum and assessment of ERK1/2 phosphorylation on hM 1 , hM 2 and hM 3 on CHO cells have shown that the new compounds are endowed with muscarinic antagonistic properties. Kinetic binding studies have revealed that some of the tested compounds are able to slow the rate of dissociation of NMS, suggesting a bitopic behavior. Docking simulations, performed on the hM 1 and hM 2 receptors, give a sound rationalization of the experimental data revealing how these compounds are able to interact with both orthosteric and allosteric binding sites depending on the length of their connecting chain. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00062952
- Volume :
- 108
- Database :
- Academic Search Index
- Journal :
- Biochemical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 114628647
- Full Text :
- https://doi.org/10.1016/j.bcp.2016.03.012