Description
Xanomeline is used as a potent and selective muscarinic type 1 and type 4 (M1/M4) receptor agonist to increase neuronal excitability. Xanomeline is used in studies of neurological disorders such as Alzheimer's disease and schizophrenia. However, development of the drug was halted due to severe cholinergic adverse effects. Currently, xanomeline-trospium (KarXT) (a peripheral cholinergic antagonist) has been explored for the treatment of schizophrenia and a New Drug Application has been filed with the FDA, with a decision on whether it will be approved or not expected on 26 September 2024.
Chemical Properties
Xanomeline Oxalate: C14H23N3OSC2H2O4. [141064-23-5]. Crystallized from acetone, melting point 148°C.
(+)-L-Tartrate: C14H23N3OSC4H6O6. [152854-19-8]. Crystallized from 2-propanol, melting point 95.5°C.
Uses
Alzheimer’s disease treatment (cholinergic agonist).
Definition
ChEBI: Xanomeline is a member of thiadiazoles and a tetrahydropyridine. It has a role as a muscarinic agonist and a serotonergic agonist.
Mechanism of action
Xanomeline's mechanism of action is is to rebalance key neurotransmitter circuits, including acetylcholine, dopamine and glutamate, which are disrupted in schizophrenia and related disorders.
in vivo
Xanomeline (0.5~3 mg/kg; s.c.; 1~3 hours) induces salivation and vomiting in some monkeys[3].
Xanomeline shows functional dopamine antagonism and an antipsychotic-like profile.
Xanomeline inhibits D-amphetamine- and ( )-apomorphine-induced behavior and do not cause extrapyramidal side effects[3].
| Animal Model: | Male Cebus apella monkeys |
| Dosage: | 0.5~3 mg/kg |
| Administration: | S.c.; 1~3 hours |
| Result: | Induced salivation and vomiting in some monkeys.
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