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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

  • Czech description

Classification

  • 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)

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

  • 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