Antipsychotic-like effect of the muscarinic acetylcholine receptor agonist BuTAC in non-human primates
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Antipsychotic-like effect of the muscarinic acetylcholine receptor agonist BuTAC in non-human primates. / Andersen, Maibritt B; Croy, Carrie Hughes; Dencker, Ditte; Werge, Thomas; Bymaster, Frank P; Felder, Christian C; Fink-Jensen, Anders.
In: PLOS ONE, Vol. 10, No. 4, e0122722, 2015, p. 1-13.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Antipsychotic-like effect of the muscarinic acetylcholine receptor agonist BuTAC in non-human primates
AU - Andersen, Maibritt B
AU - Croy, Carrie Hughes
AU - Dencker, Ditte
AU - Werge, Thomas
AU - Bymaster, Frank P
AU - Felder, Christian C
AU - Fink-Jensen, Anders
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Animals
KW - Antipsychotic Agents
KW - Behavior, Animal
KW - Cebus
KW - Male
KW - Muscarinic Agonists
KW - Primates
KW - Receptors, Muscarinic
U2 - 10.1371/journal.pone.0122722
DO - 10.1371/journal.pone.0122722
M3 - Journal article
C2 - 25880220
VL - 10
SP - 1
EP - 13
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 4
M1 - e0122722
ER -
ID: 157253839