COBENFY - A NEW ANTIPSYCHOTIC DRUG

Gabriela Majchrowicz; Mikołaj Jońca; Natasza Kurys; Szymon Litke; Katarzyna Gołacka; Aleksandra Lorent; Weronika Piekarska

doi:10.31435/ijitss.3(51).2026.6311

Authors

Gabriela Majchrowicz Medical University of Lodz Aleja T. Kościuszki 4, 90–419 Łódź, Poland https://orcid.org/0009-0007-0447-8510
Mikołaj Jońca Pomeranian Medical University, ul. Rybacka 1, 70-204 Szczecin, Poland https://orcid.org/0009-0006-4435-1138
Natasza Kurys Medical University of Lodz, Aleja T. Kościuszki 4, 90–419 Łódź, Poland https://orcid.org/0009-0005-7090-259X
Szymon Litke Medical University of Lodz Aleja T. Kościuszki 4, 90–419 Łódź, Poland https://orcid.org/0009-0006-3127-8656
Katarzyna Gołacka Pomeranian Medical University, ul. Rybacka 1, 70-204 Szczecin, Poland https://orcid.org/0009-0001-5980-2812
Aleksandra Lorent Pomeranian Medical University, ul. Rybacka 1, 70-204 Szczecin, Poland https://orcid.org/0009-0001-1378-644X
Weronika Piekarska Medical University of Lodz, Aleja T. Kościuszki 4, 90–419 Łódź, Poland https://orcid.org/0009-0004-1074-1811

DOI:

https://doi.org/10.31435/ijitss.3(51).2026.6311

Keywords:

KarXT; Schizophrenia; Antipsychotic; Cobenfy; Muscarinic Receptors; Xanomeline-Trospium; Psychotic Disorders; Muscarinic Agonist, Cholinergic Agents

Abstract

Antipsychotic medications are the cornerstone of schizophrenia treatment and are traditionally classified into first-, second, and third-generation agents according to their pharmacological properties and mechanism of action. While these drugs effectively control psychotic symptoms through dopamine receptor antagonism or partial agonism, their clinical use is frequently limited by extrapyramidal symptoms, metabolic disturbances, hyperprolactinaemia, and inadequate efficacy against negative and cognitive symptoms. Cobenfy (xanomeline–trospium), approved by the U.S. Food and Drug Administration in 2024, represents the first antipsychotic with a non-dopaminergic mechanism of action. It combines xanomeline, a centrally acting muscarinic M1/M4 receptor agonist, with trospium chloride, a peripherally acting muscarinic antagonist that reduces cholinergic adverse effects without crossing the blood–brain barrier. This review summarizes the pharmacology, mechanism of action, pharmacokinetics, clinical efficacy, safety, and therapeutic role of Cobenfy based on available preclinical and clinical evidence. Phase II and III studies, including the EMERGENT clinical program, demonstrated significant improvements in Positive and Negative Syndrome Scale scores, sustained long-term efficacy, and a favourable metabolic profile with minimal effects on body weight and cardiometabolic parameters. Preliminary findings also suggest potential benefits for negative symptoms and cognitive impairment. Rather than replacing established antipsychotics, it expands current treatment options by introducing a novel cholinergic therapeutic strategy. Ongoing comparative, long-term, and real-world studies will further define its role in schizophrenia management and its potential application in other neuropsychiatric disorders, including Alzheimer's disease–related psychosis.

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