Novel long‐acting antagonists of muscarinic ACh receptors
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F18%3A00490235" target="_blank" >RIV/67985823:_____/18:00490235 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1111/bph.14187" target="_blank" >http://dx.doi.org/10.1111/bph.14187</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1111/bph.14187" target="_blank" >10.1111/bph.14187</a>
Alternative languages
Result language
angličtina
Original language name
Novel long‐acting antagonists of muscarinic ACh receptors
Original language description
The aim of this study was to develop potent and long-acting antagonists of muscarinic ACh receptors. The 4-hexyloxy and 4-butyloxy derivatives of 1-[2-(4-oxidobenzoyloxy)ethyl]-1,2,3,6-tetrahydropyridin-1-ium were synthesized and tested for biological activity. Antagonists with long-residence time at receptors are therapeutic targets for the treatment of several neurological and psychiatric human diseases. Their long-acting effects allow for reduced daily doses and adverse effects. The binding and antagonism of functional responses to the agonist carbachol mediated by 4-hexyloxy compounds were investigated in CHO cells expressing individual subtypes of muscarinic receptors and compared with 4-butyloxy analogues. The 4-hexyloxy derivatives were found to bind muscarinic receptors with micromolar affinity and antagonized the functional response to carbachol with a potency ranging from 30 nM at M-1 to 4 mu M at M-3 receptors. Under washing conditions to reverse antagonism, the half-life of their antagonistic action ranged from 1.7 h at M-2 to 5h at M-5 receptors. The 4-hexyloxy derivatives were found to be potent long-acting M-1-preferring antagonists. In view of current literature, M-1-selective antagonists may have therapeutic potential for striatal cholinergic dystonia, delaying epileptic seizure after organophosphate intoxication or relieving depression. These compounds may also serve as a tool for research into cognitive deficits.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30105 - Physiology (including cytology)
Result continuities
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
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
British Journal of Pharmacology
ISSN
0007-1188
e-ISSN
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Volume of the periodical
175
Issue of the periodical within the volume
10
Country of publishing house
GB - UNITED KINGDOM
Number of pages
13
Pages from-to
1731-1743
UT code for WoS article
000430658800012
EID of the result in the Scopus database
2-s2.0-85045208095