Novel M-2-selective, G(i)-biased agonists of muscarinic acetylcholine receptors

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F20%3A00524282" target="_blank" >RIV/67985823:_____/20:00524282 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1111/bph.14970" target="_blank" >https://doi.org/10.1111/bph.14970</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1111/bph.14970" target="_blank" >10.1111/bph.14970</a>

Result language
angličtina
Original language name
Novel M-2-selective, G(i)-biased agonists of muscarinic acetylcholine receptors
Original language description
More than 30% of currently marketed medications act via GPCRs. Thus, GPCRs represent one of the most important pharmacotherapeutic targets. In contrast to traditional agonists activating multiple signalling pathways, agonists activating a single signalling pathway represent a new generation of drugs with increased specificity and fewer adverse effects. Two of the tested new compounds only inhibited cAMP synthesis in CHO cells, primary cultures, and native tissues, with selectivity for M2 muscarinic receptors and displaying bias towards the Gi signalling pathway at all subtypes of muscarinic receptors. Molecular modelling revealed interactions with the orthosteric binding site in a way specific for a given agonist followed by agonist-specific changes in the conformation of the receptor. The identified compounds may serve as lead structures in the search for novel non-steroidal and non-opioid analgesics acting via M2 and M4 muscarinic receptors with reduced side effects associated with activation of the phospholipase C signalling pathway.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30105 - Physiology (including cytology)

Project
<a href="/en/project/GA17-16182S" target="_blank" >GA17-16182S: Molecular basis of functional selectivity of Nsubstituted tetrahydropyridinium salts at muscarinic receptors</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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