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


METHODS
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.
Shekhar
Anantha
A
Department of Psychiatry, Indiana University School of Medicine, 1111 West 10th St., Suite 313, Indianapolis, IN 46202, USA. ashekhar@iupui.edu
Potter
William Z
WZ
Lightfoot
Jeffrey
J
Lienemann
John
J
Dubé
Sanjay
S
Mallinckrodt
Craig
C
Bymaster
Frank P
FP
McKinzie
David L
DL
Felder
Christian C
CC
D000293:Adolescent; D000328:Adult; D000339:Affect; D010054:Brief Psychiatric Rating Scale; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology; D003710:Demography; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D011950:Receptors, Cholinergic / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012559:Schizophrenia / Q000188:drug therapy* / Q000453:epidemiology; D012720:Severity of Illness Index; D013830:Thiadiazoles / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*
D018721:Muscarinic Agonists; D011725:Pyridines; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D013830:Thiadiazoles; C075257:xanomeline