Symposium
Plenary Hall
Plenary Hall
Wednesday, June 18, 02:40 PM – 03:55 PM
Symposium 16: Muscarinic M1 and M4 receptors: Drug development, a treatment for schizophrenia and a potential treatment for addiction
In 2024 the FDA approved the drug Cobenfy (KarXT) to be used in the treatment of schizophrenia. The therapeutic mechanism of action of Cobenfy is as an agonist at the muscarinic M1 and M4 receptors, which makes it the first non-dopaminergic targeting drug approved for the treatment of schizophrenia. Whilst the approval of Cobenfy for the treatment of schizophrenia may be the first clinical indication for drugs targeting muscarinic M1 and M4 receptors, a growing body of data suggest such drugs may be useful in treating other disorders, including addiction. In this symposium experts in the field will focus on progress in developing drugs targeting the muscarinic M1 and M4 receptors at the orthosteric and allosteric sites on the receptors and data from neuroimaging, human postmortem CNS and animal studies that supported the notion that such drugs would be effective in treating schizophrenia. Finally, data suggesting targeting the muscarinic M1 and M4 receptor will prove effective in treating cocaine use disorder will be reviewed.
The symposium will be opened by Dr Carrie K. Jones, from the Department of Pharmacology at Vanderbilt University, who will discuss problems in targeting the orthosteric site on different muscarinic receptors and how targeting the allosteric sites on these receptors has led to ligands with high specificity for each receptor subtype, specifically through
optimization of M1 and M4 positive allosteric modulators (PAMs). Dr. Jones will detail available pre-clinical data using these novel M1 and M4 PAMs with important implications for the broader symptomatic treatment of schizophrenia and other psychiatric disorders1-4.
Dr Brian Dean, from the Florey Institute of Neuroscience and Mental Health, will review outcomes from multiple lines of research that suggest that the muscarinic M1 and M4 receptors are affected by the molecular pathology of schizophrenia5. Dr Dean will then review progress in understanding the molecular pathology of a sub-group withing the syndrome of schizophrenia who can be separated because they have a marked loss of muscarinic M1 receptors in their cortex6. Finally, Dr Dean will show data suggesting this sub-group may not respond optimally to being treated with drugs that target the muscarinic M1 receptor7,8. To conclude the session, Dr Morgan Thomsen from Region Hovedstadens Psychiatry and the University of Copenhagen will show data suggesting the muscarinic M1 and M4 receptors are promising drug targets for the treatment of addiction9-12. Dr Thomsen will particularly focus on the work by himself and others indicating that muscarinic M1 and M4 receptors are promising targets for the treatment of cocaine addiction.
In summary, this symposium will give a comprehensive update on the process of developing drugs to activate muscarinic M1 and M4 receptors with the goal of treating disorders of the human CNS. It will detail the involvement of those two receptors in the pathology of schizophrenia and why they have proven to be effective drug targets and will point to the potential for treating other CNS disorders by activating muscarinic M1 and M4 receptors.
The symposium will be opened by Dr Carrie K. Jones, from the Department of Pharmacology at Vanderbilt University, who will discuss problems in targeting the orthosteric site on different muscarinic receptors and how targeting the allosteric sites on these receptors has led to ligands with high specificity for each receptor subtype, specifically through
optimization of M1 and M4 positive allosteric modulators (PAMs). Dr. Jones will detail available pre-clinical data using these novel M1 and M4 PAMs with important implications for the broader symptomatic treatment of schizophrenia and other psychiatric disorders1-4.
Dr Brian Dean, from the Florey Institute of Neuroscience and Mental Health, will review outcomes from multiple lines of research that suggest that the muscarinic M1 and M4 receptors are affected by the molecular pathology of schizophrenia5. Dr Dean will then review progress in understanding the molecular pathology of a sub-group withing the syndrome of schizophrenia who can be separated because they have a marked loss of muscarinic M1 receptors in their cortex6. Finally, Dr Dean will show data suggesting this sub-group may not respond optimally to being treated with drugs that target the muscarinic M1 receptor7,8. To conclude the session, Dr Morgan Thomsen from Region Hovedstadens Psychiatry and the University of Copenhagen will show data suggesting the muscarinic M1 and M4 receptors are promising drug targets for the treatment of addiction9-12. Dr Thomsen will particularly focus on the work by himself and others indicating that muscarinic M1 and M4 receptors are promising targets for the treatment of cocaine addiction.
In summary, this symposium will give a comprehensive update on the process of developing drugs to activate muscarinic M1 and M4 receptors with the goal of treating disorders of the human CNS. It will detail the involvement of those two receptors in the pathology of schizophrenia and why they have proven to be effective drug targets and will point to the potential for treating other CNS disorders by activating muscarinic M1 and M4 receptors.