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

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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.

Original languageEnglish
Article numbere0122722
JournalPLOS ONE
Volume10
Issue number4
Pages (from-to)1-13
Number of pages13
ISSN1932-6203
DOIs
Publication statusPublished - 2015

    Research areas

  • Animals, Antipsychotic Agents, Behavior, Animal, Cebus, Male, Muscarinic Agonists, Primates, Receptors, Muscarinic

ID: 157253839