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

Anantha Shekhar, William Z. Potter, Jeffrey Lightfoot, John Lienemann, Sanjay Dubé, Craig Mallinckrodt, Frank P. Bymaster, David L. McKinzie, Christian C. Felder

Research output: Contribution to journalArticle

278 Citations (Scopus)

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 (M1 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.

Original languageEnglish
Pages (from-to)1033-1039
Number of pages7
JournalAmerican Journal of Psychiatry
Volume165
Issue number8
DOIs
StatePublished - Aug 2008

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xanomeline
Muscarinic Agonists
Muscarinic Receptors
Schizophrenia
Brief Psychiatric Rating Scale
Cognition
Therapeutics
Placebos
Verbal Learning
Short-Term Memory
Cholinergic Agents

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Shekhar, A., Potter, W. Z., Lightfoot, J., Lienemann, J., Dubé, S., Mallinckrodt, C., ... Felder, C. C. (2008). Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. American Journal of Psychiatry, 165(8), 1033-1039. https://doi.org/10.1176/appi.ajp.2008.06091591

Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. / Shekhar, Anantha; Potter, William Z.; Lightfoot, Jeffrey; Lienemann, John; Dubé, Sanjay; Mallinckrodt, Craig; Bymaster, Frank P.; McKinzie, David L.; Felder, Christian C.

In: American Journal of Psychiatry, Vol. 165, No. 8, 08.2008, p. 1033-1039.

Research output: Contribution to journalArticle

Shekhar, A, Potter, WZ, Lightfoot, J, Lienemann, J, Dubé, S, Mallinckrodt, C, Bymaster, FP, McKinzie, DL & Felder, CC 2008, 'Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia', American Journal of Psychiatry, vol. 165, no. 8, pp. 1033-1039. https://doi.org/10.1176/appi.ajp.2008.06091591
Shekhar, Anantha ; Potter, William Z. ; Lightfoot, Jeffrey ; Lienemann, John ; Dubé, Sanjay ; Mallinckrodt, Craig ; Bymaster, Frank P. ; McKinzie, David L. ; Felder, Christian C. / Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. In: American Journal of Psychiatry. 2008 ; Vol. 165, No. 8. pp. 1033-1039.
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