Selective Muscarinic Receptor Agonist Xanomeline as a Novel Treatment Approach for Schizophrenia

TLDR: Results support further investigation of xanomeline as a novel approach to treating schizophrenia and show improvements most robustly in measures of verbal learning and short-term memory function.

Abstract: Objective: There are significant unmet needs in the treatment of schizophrenia, especially for the treatment of cognitive impairment, negative syndrome, and cognitive function. Preclinical data suggest that agonists with selective affinity for acetylcholine muscarinic receptors provide a potentially new mechanism to treat schizophrenia. The authors studied xanomeline, a relatively selective muscarinic type 1 and type 4 (M 1 and M 4 ) receptor agonist, to determine if this agent is effective in the treatment of schizophrenia. Method: In this pilot study, the authors examined the efficacy of xanomeline on clinical outcomes in subjects with schizophrenia (N=20) utilizing a double-blind, placebo-controlled, 4-week treatment design. Outcome measures included the Positive and Negative Syndrome Scale (PANSS) for schizophrenia, the Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression (CGI) scale, and a test battery designed to measure cognitive function in patients with schizophrenia. Results: Su...