Journal article

Assessment of the Molecular Mechanisms of Action of Novel 4-Phenylpyridine-2-One and 6-Phenylpyrimidin-4-One Allosteric Modulators at the M-1 Muscarinic Acetylcholine Receptors

Emma T van der Westhuizen, Arthur Spathis, Elham Khajehali, Manuela Jorg, Shailesh N Mistry, Ben Capuano, Andrew B Tobin, Patrick M Sexton, Peter J Scammells, Celine Valant, Arthur Christopoulos

MOLECULAR PHARMACOLOGY | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS | Published : 2018

Abstract

Positive allosteric modulators (PAMs) that target the M1 muscarinic acetylcholine (ACh) receptor (M1 mAChR) are potential treatments for cognitive deficits in conditions such as Alzheimer disease and schizophrenia. We recently reported novel 4-phenylpyridine-2-one and 6-phenylpyrimidin-4-one M1 mAChR PAMs with the potential to display different modes of positive allosteric modulation and/or agonism but whose molecular mechanisms of action remain undetermined. The current study compared the pharmacology of three such novel PAMs with the prototypical first-generation PAM, benzyl quinolone carboxylic acid (BQCA), in a recombinant Chinese hamster ovary (CHO) cell line stably expressing the human..

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Grants

Awarded by National Health and Medical Research Council Program


Funding Acknowledgements

This work was supported by National Health and Medical Research Council Program Grant [APP1055134]. A.C. is a senior principal and P.M.S. a principal research fellow of the National Health and Medical Research Council of Australia. C.V. is supported by a Future Fellowship from the Australian Research Council. E.T.v.d.W. is supported by an Early Career Fellowship from the National Health and Medical Research Council of Australia.