Current antipsychotic medicines rely on the same primary pathway and approach of inhibiting D2 dopamine receptors, and frequently 5HT-52A serotonin receptors, and are often used by physicians to address a wide range of psychiatric conditions, including schizophrenia and bipolar disorder, among others.
While these medicines have been the standard of care for many years, people living with psychiatric conditions, such as schizophrenia, their doctors, and researchers have been looking for alternatives to improve treatment outcomes.
This has led to interest in investigating treatments that work through different neurotransmitters such as acetylcholine, located in the cholinergic pathway. Within the cholinergic pathway, acetylcholine interacts with a type of receptor called the muscarinic receptor. There are five distinct muscarinic receptors, M1-M5, found in the brain as well as various peripheral tissues.
Muscarinic receptor agonists emerged in the 1990s as a promising new approach for treating psychosis and cognitive impairment. The link between muscarinic receptor stimulation in the central nervous system (CNS), particularly the stimulation of M1 and M4 receptors, and the reduction of symptoms of psychosis and improvement in cognition, has been well studied and is supported by research from preclinical studies and clinical trials. However, the successful development of a therapy targeting muscarinic receptors has been limited by undesirable side effects that are believed to arise primarily as a result of stimulation of muscarinic receptors in peripheral tissues.