title: Antipsychotic-like effect of the muscarinic acetylcholine receptor agonist BuTAC in non-human primates.
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.
authors.affiliation: Research Institute of Biological Psychiatry, Sct. Hans Hospital, Roskilde, Denmark.
authors.forename: Maibritt B
authors.initials: MB
authors.lastname: Andersen
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
authors.forename: Carrie Hughes
authors.initials: CH
authors.lastname: Croy
authors.affiliation: Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark; Psychiatric Centre Copenhagen, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ditte
authors.initials: D
authors.lastname: Dencker
authors.affiliation: Research Institute of Biological Psychiatry, Sct. Hans Hospital, Roskilde, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
authors.affiliation: Euthymics Bioscience Inc, 43 Thorndike St Suite 1-3, Cambridge, Massachusetts, United States of America.
authors.forename: Frank P
authors.initials: FP
authors.lastname: Bymaster
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
authors.forename: Christian C
authors.initials: CC
authors.lastname: Felder
authors.affiliation: Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark; Psychiatric Centre Copenhagen, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Fink-Jensen
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal; D002428:Cebus; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D011323:Primates; D011976:Receptors, Muscarinic / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic