New schizophrenia drug could treat Alzheimer’s disease

Kwon, D. (2024, November 21). New schizophrenia drug could treat Alzheimer’s disease: Half a dozen drugs are in trials for conditions of the brain, but success is not guaranteed. Nature News.        

Credits for Summary: Khyati Shukla Aakash Khurana

A new wave of psychiatric drugs is emerging, led by KarXT, a novel schizophrenia medication that targets muscarinic receptors rather than relying on traditional dopamine-blocking mechanisms. KarXT, sold as Cobenfy, represents a significant shift in psychiatric treatment, offering both antipsychotic and cognitive benefits. Its development, combining xanomeline with trospium to mitigate side effects, has renewed interest in muscarinic-targeted therapies. However, the success of KarXT and similar drugs is not guaranteed, as challenges persist in clinical trials, as highlighted by the recent failure of Abbvie’s emraclidine to outperform a placebo.

KarXT primarily interacts with the M1 and M4 muscarinic receptors, with M4 linked to antipsychotic effects and M1 associated with cognitive improvements. This dual-action mechanism distinguishes it from other muscarinic drugs, which often focus on single receptor types. Researchers are also exploring allosteric modulators to enhance selectivity and minimize side effects. While KarXT’s promising results have sparked optimism, its real-world performance remains uncertain, as seen in follow-up studies where a notable percentage of patients discontinued the drug due to side effects.

Beyond schizophrenia, muscarinic drugs hold potential for other neurological and psychiatric conditions. Trials are underway to assess KarXT’s efficacy in treating Alzheimer’s disease-related psychosis and bipolar disorder. Additionally, M1-targeting drugs are being studied for their ability to mitigate cognitive decline and potentially slow Alzheimer’s progression. Researchers are also investigating muscarinic pathways in addiction and movement disorders like Parkinson's disease. Despite the challenges, the re-emergence of muscarinic-targeted therapies marks a hopeful chapter for advancing brain disorder treatments.