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- Title
Antipsychotic-Like Effect of the Muscarinic Acetylcholine Receptor Agonist BuTAC in Non-Human Primates.
- Authors
Andersen, Maibritt B.; Croy, Carrie Hughes; Dencker, Ditte; Werge, Thomas; Bymaster, Frank P.; Felder, Christian C.; Fink-Jensen, Anders
- Abstract
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.
- Subjects
ANTIPSYCHOTIC agents; MUSCARINIC acetylcholine receptors; DOPAMINE antagonists; SCHIZOPHRENIA treatment; DRUG abuse; PRIMATES as laboratory animals
- Publication
PLoS ONE, 2015, Vol 10, Issue 4, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0122722