Xanomeline tartrate

Xanomeline (LY 246708) is the potent agonist of muscarinic M1/M4 receptor with antipsychotic-like activity. Xanomeline (LY 246708) increases neuronal excitability. Xanomeline (LY 246708) can be used for the research of schizophrenia[1][2][3].

Signaling Pathways >> Neuronal Signaling >> mAChR

Signaling Pathways >> GPCR/G Protein >> mAChR

Research Areas >> Neurological Disease

M1/M4[1]

Xanomeline (LY 246708) (0.1-10 μM; CNS4U) shows an overall increase in the mean firing rate. Xanomeline (LY 246708) shows the M1 receptor is functional in hiPSC derived neurons. Xanomeline (LY 246708) (＞1 μM) has a prolonged engagement with the receptor and produces a persistent receptor activation leading to a sustained suppression of the M-current[1].

Xanomeline (LY 246708) (0.5-3 mg/kg; s.c.; 1-3 hours) induces salivation and vomiting in some monkeys[3]. Xanomeline (LY 246708) shows functional dopamine antagonism and an antipsychotic-like profile[3]. Xanomeline (LY 246708) inhibits D-amphetamine- and (−)-apomorphine-induced behavior and do not cause extrapyramidal side effects[3]. Animal Model: Male Cebus apella monkeys[3] Dosage: 0.5-3 mg/kg Administration: s.c.; 1-3 hours Result: Induced salivation and vomiting in some monkeys.

[1]. Kreir M, et al. Role of Kv7.2/Kv7.3 and M1 muscarinic receptors in the regulation of neuronal excitability in hiPSC-derived neurons. Eur J Pharmacol. 2019;858:172474.

[2]. Shekhar A, et al. Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. Am J Psychiatry. 2008;165(8):1033-1039.

[3]. Andersen MB, et al. The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys. Neuropsychopharmacology. 2003;28(6):1168-1175.