Current advances in allosteric modulation of muscarinic receptors

Jan Jakubik, Esam E. El-Fakahany

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Allosteric modulators are ligands that bind to a site on the receptor that is spatially separated from the orthosteric binding site for the endogenous neurotransmitter. Allosteric modulators modulate the binding affinity, potency, and efficacy of orthosteric ligands. Muscarinic acetylcholine receptors are prototypical allosterically-modulated G-protein-coupled receptors. They are a potential therapeutic target for the treatment of psychiatric, neurologic, and internal diseases like schizophrenia, Alzheimer’s disease, Huntington disease, type 2 diabetes, or chronic pulmonary obstruction. Here, we reviewed the progress made during the last decade in our understanding of their mechanisms of binding, allosteric modulation, and in vivo actions in order to understand the translational impact of studying this important class of pharmacological agents. We overviewed newly developed allosteric modulators of muscarinic receptors as well as new spin-off ideas like bitopic ligands combining allosteric and orthosteric moieties and photo-switchable ligands based on bitopic agents.

Original languageEnglish (US)
Article number325
Issue number2
StatePublished - Feb 2020

Bibliographical note

Funding Information:
Funding: This research was funded by the Czech Academy of Sciences institutional support [RVO:67985823] and the Grant Agency of the Czech Republic grant [19-05318S].

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.


  • Acetylcholine
  • Allosteric modulation
  • Muscarinic receptors

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