Ligand bias at the muscarinic acetylcholine receptor family: Opportunities and challenges

Kaoullas, Michaela G.; Thal, David M.; Christopoulos, Arthur; Valant, Celine

doi:10.1016/j.neuropharm.2024.110092

Neuropharmacology

2024

DOI: 10.1016/j.neuropharm.2024.110092

|View full text |Cite

Ligand bias at the muscarinic acetylcholine receptor family: Opportunities and challenges

Michaela G. Kaoullas,

David M. Thal,

Arthur Christopoulos

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Article1

Relationship

Self Cite0

Independent1

Authors

Journals

Cited by 1 publication

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

The potential of muscarinic M1 and M4 receptor activators for the treatment of cognitive impairment associated with schizophrenia

Yohn,

Harvey,

Brannan

et al. 2024

Front. Psychiatry

View full text Add to dashboard Cite

Cognitive impairment is a core symptom of schizophrenia and a major determinant of poor long-term functional outcomes. Despite considerable efforts, we do not yet have any approved pharmacological treatments for cognitive impairment associated with schizophrenia (CIAS). A combination of advances in pre-clinical research and recent clinical trial findings have led to a resurgence of interest in the cognition-enhancing potential of novel muscarinic acetylcholine receptor (mAChR) agonists in schizophrenia. This article provides an overview of the scientific rationale for targeting M1 and M4 mAChRs. We describe the evolution of neuroscience research on these receptors since early drug discovery efforts focused on the mAChR agonist xanomeline. This work has revealed that M1 and M4 mAChRs are highly expressed in brain regions that are implicated in cognition. The functional significance of M1 and M4 mAChRs has been extensively characterized in animal models via use of selective receptor subtype compounds through neuronal and non-neuronal mechanisms. Recent clinical trials of a dual M1/M4 mAChR agonist show promising, replicable evidence of potential pro-cognitive effects in schizophrenia, with several other mAChR agonists in clinical development.

show abstract

The potential of muscarinic M1 and M4 receptor activators for the treatment of cognitive impairment associated with schizophrenia

Yohn,

Harvey,

Brannan

et al. 2024

Front. Psychiatry

View full text Add to dashboard Cite

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Ligand bias at the muscarinic acetylcholine receptor family: Opportunities and challenges

Cited by 1 publication

References 102 publications

The potential of muscarinic M1 and M4 receptor activators for the treatment of cognitive impairment associated with schizophrenia

The potential of muscarinic M1 and M4 receptor activators for the treatment of cognitive impairment associated with schizophrenia

Contact Info

Product

Resources

About