Scientists uncover new and “unexpected” information about schizophrenia drug
14 September 2023
Cryo-EM map of the M4 mAChR in complex with G proteins bound to xanomeline. Nature Communications
Drug discovery researchers from Monash University have uncovered new, and unexpected, information about ‘xanomeline’, a potential-first-in class drug currently progressing through Phase III clinical trials for the treatment of patients with schizophrenia.
Xanomeline has a rich clinical history in neuropsychopharmacology, and prior studies of its ‘atypical’ pharmacology had highlighted the potential role of specific subtypes of the muscarinic acetylcholine receptor (mAChR) family of G protein-coupled receptors (GPCRs) in its potential therapeutic effects.
Xanomeline activates mAChRs in the brain, especially the M4 mAChR subtype, which regulates neurotransmitters, such as dopamine and glutamate, known to be imbalanced in people living with neuropsychiatric and neurological diseases, including schizophrenia.
The new study, published in the prestigious journal, Nature Communications, was led by Dr David Thal, Dr Celine Valant and Professor Arthur Christopoulos from the Monash Institute of Pharmaceutical Sciences (MIPS), and Associate Professor Ron Dror, from Stanford University.