xanomeline + trospium chloride (Karuna Therapeutics)

xanomeline + trospium chloride (Cobenfy, formerly KarXT) is a first-in-class, orally administered antipsychotic combination of xanomeline, a dual M1/M4-preferring muscarinic acetylcholine receptor agonist, and trospium chloride, a peripherally restricted pan-muscarinic receptor antagonist. Developed by Bristol Myers Squibb following its acquisition of Karuna Therapeutics, Cobenfy represents a paradigm shift in the treatment of schizophrenia as the first approved antipsychotic that does not directly target dopamine D2 receptors. Xanomeline acts centrally to stimulate M1 and M4 receptors, which indirectly modulates dopaminergic transmission and improves positive, negative, and cognitive symptoms of schizophrenia. Trospium chloride, which does not cross the blood-brain barrier, is co-formulated to block peripheral muscarinic receptors, thereby mitigating the dose-limiting peripheral cholinergic side effects (such as nausea, vomiting, and diarrhea) associated with xanomeline alone. Cobenfy is approved in the United States for the treatment of schizophrenia in adults and is in Phase 3 development for other neuropsychiatric indications, including Alzheimer's disease psychosis, Alzheimer's disease agitation, and manic episodes in bipolar I disorder.

Brand names

Cobenfy

Other names

xanomeline and trospium chloridexanomeline/trospiumxanomeline/trospium chloride