Azasetron HCl (formerly Y 25130 HCl; Y-25130; Y25130), an approved antiemetic drug, is a potent and selective antagonist of 5-HT3 receptor with an IC50 of 0.33 nM. It is an antiemetic medication that is mainly used to treat nausea and vomiting brought on by cancer chemotherapy.

Physicochemical Properties

Molecular Formula	C17H21CL2N3O3
Molecular Weight	386.2729
Exact Mass	385.1
Elemental Analysis	C, 52.86; H, 5.48; Cl, 18.35; N, 10.88; O, 12.43
CAS #	123040-16-4
Related CAS #	123040-69-7; 2025360-91-0 (besylate); 123040-16-4 (HCl)
PubChem CID	115000
Appearance	White to off-white solid powder
Boiling Point	558ºC at 760 mmHg
Flash Point	291.2ºC
LogP	2.72
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	25
Complexity	523
Defined Atom Stereocenter Count	0
InChi Key	DBMKBKPJYAHLQP-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H20ClN3O3.ClH/c1-20-14-7-11(18)6-12(16(14)24-9-15(20)22)17(23)19-13-8-21-4-2-10(13)3-5-21;/h6-7,10,13H,2-5,8-9H2,1H3,(H,19,23);1H
Chemical Name	N-(1-azabicyclo[2.2.2]octan-3-yl)-6-chloro-4-methyl-3-oxo-1,4-benzoxazine-8-carboxamide;hydrochloride
Synonyms	Y 25130 HCl; Y-25130; Azasetron HCl; 123040-69-7; Serotone; 141922-90-9; Y-25130 hydrochloride; Azasetron (hydrochloride); Y25130; Azasetron HCl; Azasetron hydrochloride
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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	5-HT3 Receptor ( IC50 = 0.33 nM )
ln Vitro	In this study, researchers describe the 5-hydroxytryptamine3 (5-HT3) receptor antagonism of Y-25130 ((+-)-N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro-4-methyl-3-oxo-3,4-dih yd ro- 2H-1,4-benzoxazine-8-carboxamide monohydrochloride) in the rat cerebral cortex, isolated rabbit heart and isolated guinea pig ileum. In an in vitro binding assay, Y-25130 inhibited the specific binding of [3H]quipazine to 5-HT3 receptors at the synaptic membranes of the rat cerebral cortex with a Ki value of 2.9 nM, the same as that of ondansetron. Metoclopramide, 5-HT and 2-methyl-5-HT also showed an inhibitory effect, but their affinities for 5-HT3 receptors were lower than that of Y-25130. Y-25130 showed low affinity for histamine H1 receptors (IC50 = 4.4 microM) but it could not reveal any affinities for the other receptors (5-HT1A, 5-HT2, dopamine D1, dopamine D2, alpha 1-adrenoceptor, alpha 2-adrenoceptor, muscarine and benzodiazepine) even at a 10 microM concentration. In the isolated rabbit heart, Y-25130 antagonized the indirect sympathomimetic responses to 5-HT (pA2 value = 10.06) and this effect was more potent than that of metoclopramide. In the isolated longitudinal smooth muscle of the guinea pig ileum, concentration-contraction effect curves for 5-HT were biphasic in the presence of ketanserin. Y-25130 shifted to the right only in the second phase of concentration-effect curves for 5-HT (pA2 value = 7.04) and its activity was more potent than that of metoclopramide. These results indicate that Y-25130 is a potent and selective 5-HT3 receptor antagonist[1].
ln Vivo	Azasetron has the ability to enter the systemic circulation by effectively penetrating the skin[2]. For in vivo studies, azasetron pharmacokinetic parameters in Bama miniature pigs were determined according to a noncompartment model method after topical application of transdermal patches and intravenous administration of azasetron injections. The best permeation profile was obtained with the formulation containing DURO-TAK 87-9301 as adhesive, 5% of isopropyl myristate as penetration enhancer, and 5% of azasetron. The optimal patch formulation exhibited sustained release profiles in vivo for 216 h. The in vivo absorption curve in Bama miniature pigs obtained by deconvolution approach using WinNonlin® program was correlated well with the in vitro permeation curve of the azasetron patch.[2]
Animal Protocol	Four male Bama miniature pigs weighing 9-11 kg (15-16 weeks old) 0.5 mg/kg I.V. administration via the abdominal vein.
References	[1]. Antagonistic activity of Y-25130 on 5-HT3 receptors. Jpn J Pharmacol, 1992. 59(4): p. 443-8. [2]. The effects of orally administered Y-25130, a selective serotonin3-receptor antagonist, on chemotherapeutic agent-induced emesis. Jpn J Pharmacol, 1993. 63(3): p. 377-83.
Additional Infomation	Azasetron hydrochloride is a benzoxazine.

Solubility Data

Solubility (In Vitro)	DMSO: ~2.2 mg/mL (~5.8 mM Water: ~3 mg/mL (~7.8 mM) Ethanol: <1 mg/mL
Solubility (In Vivo)	Solubility in Formulation 1: 50 mg/mL (129.44 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5889 mL	12.9443 mL	25.8886 mL
	5 mM	0.5178 mL	2.5889 mL	5.1777 mL
	10 mM	0.2589 mL	1.2944 mL	2.5889 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.