Antipsychotic-like effect of the muscarinic acetylcholine receptor agonist BuTAC in non-human primates. 2015

Maibritt B Andersen, and Carrie Hughes Croy, and Ditte Dencker, and Thomas Werge, and Frank P Bymaster, and Christian C Felder, and Anders Fink-Jensen
Research Institute of Biological Psychiatry, Sct. Hans Hospital, Roskilde, Denmark.

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.

UI MeSH Term Description Entries
D008297 Male Males
D011323 Primates An order of mammals consisting of more than 300 species that include LEMURS; LORISIDAE; TARSIERS; MONKEYS; and HOMINIDS. They are characterized by a relatively large brain when compared with other terrestrial mammals, forward-facing eyes, the presence of a CALCARINE SULCUS, and specialized MECHANORECEPTORS in the hands and feet which allow the perception of light touch. Primate
D011976 Receptors, Muscarinic One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology. Muscarinic Acetylcholine Receptors,Muscarinic Receptors,Muscarinic Acetylcholine Receptor,Muscarinic Receptor,Acetylcholine Receptor, Muscarinic,Acetylcholine Receptors, Muscarinic,Receptor, Muscarinic,Receptor, Muscarinic Acetylcholine,Receptors, Muscarinic Acetylcholine
D002428 Cebus A genus of the family CEBIDAE, subfamily CEBINAE, consisting of gracile or untufted capuchin species. Tufted capuchins belong to genus SAPAJUS. Members include C. capucinus, C. nigrivultatus, and C. albifrons. Cebus inhabits the forests of Central and South Americas. Cebu,Gracile Capuchins,Monkey, Capuchin,Monkey, Ring-Tail,Monkey, Ringtail,Monkey, Ringtailed,Untufted Capuchins,White-Fronted Capuchin,Monkey, Ring-Tailed,Capuchin Monkey,Capuchin Monkeys,Capuchin, Gracile,Capuchin, Untufted,Capuchin, White-Fronted,Gracile Capuchin,Monkey, Ring Tail,Monkey, Ring Tailed,Ring-Tail Monkey,Ring-Tail Monkeys,Ring-Tailed Monkey,Ring-Tailed Monkeys,Ringtail Monkey,Ringtail Monkeys,Ringtailed Monkey,Ringtailed Monkeys,Untufted Capuchin,White Fronted Capuchin,White-Fronted Capuchins
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors
D014150 Antipsychotic Agents Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. Antipsychotic,Antipsychotic Agent,Antipsychotic Drug,Antipsychotic Medication,Major Tranquilizer,Neuroleptic,Neuroleptic Agent,Neuroleptic Drug,Neuroleptics,Tranquilizing Agents, Major,Antipsychotic Drugs,Antipsychotic Effect,Antipsychotic Effects,Antipsychotics,Major Tranquilizers,Neuroleptic Agents,Neuroleptic Drugs,Tranquillizing Agents, Major,Agent, Antipsychotic,Agent, Neuroleptic,Drug, Antipsychotic,Drug, Neuroleptic,Effect, Antipsychotic,Major Tranquilizing Agents,Major Tranquillizing Agents,Medication, Antipsychotic,Tranquilizer, Major
D018721 Muscarinic Agonists Drugs that bind to and activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate. Cholinergic Agonists, Muscarinic,Cholinergic Agonist, Muscarinic,Cholinergic Muscarinic Agonists,Muscarinic Agonist,Agonist, Muscarinic,Agonist, Muscarinic Cholinergic,Agonists, Cholinergic Muscarinic,Agonists, Muscarinic,Agonists, Muscarinic Cholinergic,Muscarinic Agonists, Cholinergic,Muscarinic Cholinergic Agonist,Muscarinic Cholinergic Agonists

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