Investigating the Pharmacology and Therapeutic Potential of Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators

Alzheimer’s disease is a progressive neurodegenerative condition and the leading cause of dementia, which affects approximately 55 million people worldwide. There are no safe, effective and readily available disease-modifying therapies for Alzheimer’s disease, representing a significant unmet clinical need. This thesis aimed to interrogate the pharmacology and therapeutic potential of metabotropic glutamate receptor 5 negative allosteric modulators, which are promising new medicines for Alzheimer’s disease and related mood disorders. Collectively, these studies reveal previously unappreciated insights into the translational limitations hindering clinical progression, and may accelerate rational drug discovery of safer and more effective precision medicines.