Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia

Am J Psychiatry. 2008 Aug;165(8):1033-9. doi: 10.1176/appi.ajp.2008.06091591. Epub 2008 Jul 1.


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: Subjects treated with xanomeline did significantly better than subjects in the placebo group on total BPRS scores and total PANSS scores. In the cognitive test battery, subjects in the xanomeline group showed improvements most robustly in measures of verbal learning and short-term memory function.

Conclusions: These results support further investigation of xanomeline as a novel approach to treating schizophrenia.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Affect
  • Brief Psychiatric Rating Scale
  • Cognition Disorders / diagnosis
  • Cognition Disorders / epidemiology
  • Demography
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscarinic Agonists / adverse effects
  • Muscarinic Agonists / pharmacology*
  • Muscarinic Agonists / therapeutic use*
  • Neuropsychological Tests
  • Pyridines / adverse effects
  • Pyridines / pharmacology*
  • Pyridines / therapeutic use*
  • Receptors, Cholinergic / drug effects
  • Receptors, Muscarinic / drug effects*
  • Schizophrenia / drug therapy*
  • Schizophrenia / epidemiology
  • Severity of Illness Index
  • Thiadiazoles / adverse effects
  • Thiadiazoles / pharmacology*
  • Thiadiazoles / therapeutic use*


  • Muscarinic Agonists
  • Pyridines
  • Receptors, Cholinergic
  • Receptors, Muscarinic
  • Thiadiazoles
  • xanomeline