Xanomeline increases neuronal excitability as a potent and specific muscarinic type 1 and 4 (M1/M4) receptor agonist. Xanomeline may be used in research into neurological disorders such as schizophrenia.

Physicochemical Properties

Molecular Formula	C14H23N3OS
Molecular Weight	281.42
Exact Mass	281.156
CAS #	131986-45-3
Related CAS #	Xanomeline tartrate;152854-19-8;Xanomeline oxalate;141064-23-5
PubChem CID	60809
Appearance	White to yellow solid powder
Density	1.101 g/cm3
Boiling Point	397ºC at 760 mmHg
Flash Point	193.9ºC
Vapour Pressure	1.64E-06mmHg at 25°C
Index of Refraction	1.537
LogP	3.154
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	7
Heavy Atom Count	19
Complexity	298
Defined Atom Stereocenter Count	0
InChi Key	JOLJIIDDOBNFHW-UHFFFAOYSA-N
InChi Code	InChI=1S/C14H23N3OS/c1-3-4-5-6-10-18-14-13(15-19-16-14)12-8-7-9-17(2)11-12/h8H,3-7,9-11H2,1-2H3
Chemical Name	3-hexoxy-4-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)-1,2,5-thiadiazole
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	mAChR1 mAChR4
ln Vitro	The mean firing rate increased overall in response to xanomeline (0.1~10 μM; CNS4U). The functionality of M1 receptors in neurons produced from hiPSCs is demonstrated by xanomeline. When xanomeline (>1 μM) attaches to receptors, it activates them for an extended amount of time, which keeps the M current from flowing [1].
ln Vivo	In certain monkeys, xanomeline (0.5~3 mg/kg; sc; 1~3 hours) induces vomiting and salivation[3]. Xanomeline exhibits properties resembling those of an antipsychotic and functional dopamine antagonist. Xanomeline prevents extrapyramidal side effects while blocking behaviors brought on by D-amphetamine and ()-apomorphine[3].
Animal Protocol	Animal/Disease Models: Male Cebus apella monkeys Doses: 0.5~3 mg/kg Route of Administration: Sc; 1~3 hrs (hours) Experimental Results: Induced salivation and vomiting in some monkeys.
References	[1]. 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]. Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. Am J Psychiatry. 2008;165(8):1033-1039. [3]. The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys. Neuropsychopharmacology. 2003;28(6):1168-1175.
Additional Infomation	Xanomeline is a member of thiadiazoles and a tetrahydropyridine. It has a role as a muscarinic agonist and a serotonergic agonist. Xanomeline is under investigation in clinical trial NCT02831231 (Pilot Study Comparing Effects of Xanomeline Alone to Xanomeline Plus Trospium). Xanomeline is a Cholinergic Muscarinic Agonist. The mechanism of action of xanomeline is as a Cholinergic Muscarinic Agonist, and Cytochrome P450 3A4 Inhibitor, and P-Glycoprotein Inhibitor.

Solubility Data

Solubility (In Vitro)

DMSO: 50 mg/mL (177.67 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.88 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (8.88 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (8.88 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.5534 mL	17.7670 mL	35.5341 mL
	5 mM	0.7107 mL	3.5534 mL	7.1068 mL
	10 mM	0.3553 mL	1.7767 mL	3.5534 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.