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PLoS One. 2015 Apr 16;10(4):e0122722. doi: 10.1371/journal.pone.0122722. eCollection 2015.

Antipsychotic-like effect of the muscarinic acetylcholine receptor agonist BuTAC in non-human primates.

Author information

Research Institute of Biological Psychiatry, Sct. Hans Hospital, Roskilde, Denmark.
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark; Psychiatric Centre Copenhagen, University of Copenhagen, Copenhagen, Denmark.
Euthymics Bioscience Inc, 43 Thorndike St Suite 1-3, Cambridge, Massachusetts, United States of America.


Cholinergic, muscarinic receptor agonists exhibit functional dopamine antagonism and muscarinic receptors have been suggested as possible future targets for the treatment of schizophrenia and drug abuse. The muscarinic ligand (5R,6R)-6-(3-butylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3.2.1]octane (BuTAC) exhibits high affinity for muscarinic receptors with no or substantially less affinity for a large number of other receptors and binding sites, including the dopamine receptors and the dopamine transporter. In the present study, we wanted to examine the possible antipsychotic-like effects of BuTAC in primates. To this end, we investigated the effects of BuTAC on d-amphetamine-induced behaviour in antipsychotic-naive Cebus paella monkeys. Possible adverse events of BuTAC, were evaluated in the same monkeys as well as in monkeys sensitized to antipsychotic-induced extrapyramidal side effects. The present data suggests that, the muscarinic receptor ligand BuTAC exhibits antipsychotic-like behaviour in primates. The behavioural data of BuTAC as well as the new biochemical data further substantiate the rationale for the use of muscarinic M1/M2/M4-preferring receptor agonists as novel pharmacological tools in the treatment of schizophrenia.

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