| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| 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 |
In preclinical pharmacokinetic studies, male Bama miniature pigs weighing 9-11 kg and aged 15-16 weeks were used to investigate a transdermal delivery system for Azasetron. Animals received an intravenous injection of 0.5 mg/kg Azasetron via the abdominal vein as a control. Transdermal patches containing different formulations (5% Azasetron, 5% isopropyl myristate as a permeation enhancer, and DURO-TAK 87-9301 as a pressure-sensitive adhesive) were applied to the depilated dorsal skin. Non-compartmental analysis was used to determine the pharmacokinetic parameters of Azasetron. The optimal patch formulation demonstrated sustained release characteristics in vivo for up to 216 hours.
In rat absorption, distribution, and excretion studies, Azasetron labeled with 14C was administered orally at doses of 0.4, 2, and 10 mg/kg. The drug was primarily absorbed from the small intestine (absorption rate >91%), reaching peak plasma concentrations within 0.6 hours after administration. The terminal half-life ranged from 6.7 to 8.0 hours. Radioactivity was essentially completely eliminated from the body within 96 hours after administration.
In a cisplatin-induced ototoxicity model using rats, the besylate salt form of Azasetron, R-Azasetron besylate (SENS-401), was administered orally at doses of 6.6, 13.2, and 26.4 mg/kg/day for 14 consecutive days. Treatment dose-dependently improved auditory brainstem response thresholds (maximum improvement of 30 dB) and distortion product otoacoustic emission amplitudes (maximum improvement of 19 dB). The treatment also significantly increased the survival count of outer hair cells in the cochlea (up to an 11-fold increase in the basal turn).
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 |
This study aimed to develop an azasetron transdermal drug delivery system and evaluate the correlation between its in vitro and in vivo release. In vitro experiments were conducted using a two-compartment diffusion cell to investigate the effects of different binders, penetration enhancers, and azasetron loading on the transdermal penetration of azasetron in the patch in rabbits. In in vivo experiments, pharmacokinetic parameters of the transdermal patch and azasetron were determined in Bama miniature pigs using a non-compartmental model. The results showed that the formulation using DURO-TAK 87-9301 as the binder, 5% isopropyl myristate as the penetration enhancer, and 5% azasetron as the active ingredient exhibited the best permeability. This optimal patch formulation achieved sustained release in vivo for up to 216 hours. The in vivo absorption curve in Bama miniature pigs obtained using deconvolution analysis with the WinNonlin® program showed good correlation with the in vitro permeation curve of the azasetron patch. These results indicate that the developed azasetron patch holds promise for treating chemotherapy-induced delayed nausea and vomiting, and that in vitro skin permeation experiments can be used to predict the in vivo performance of the transdermal azasetron patch. [2]
To provide a better route of administration, azasetron was formulated as a transdermal patch. The optimal formulation for in vitro skin penetration testing contained DURO-TAK® 87-9301 (National Starch Chemical Company, USA), 5% promethazine, and 5% azasetron. In vitro and in vivo porcine skin penetration profiles showed that azasetron effectively penetrated the skin and entered the systemic circulation. [2] |
| Molecular Formula |
C17H20CLN3O3
|
|---|---|
| Exact Mass |
349.119
|
| CAS # |
2025360-90-9
|
| Related CAS # |
123040-69-7 (HCl);2025360-90-9;2025360-91-0 (besylate);
|
| PubChem CID |
25271863
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
1.6
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
24
|
| Complexity |
523
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
CN1C(=O)COC2=C(C=C(C=C21)Cl)C(=O)N[C@H]3CN4CCC3CC4
|
| InChi Key |
WUKZPHOXUVCQOR-ZDUSSCGKSA-N
|
| InChi Code |
InChI=1S/C17H20ClN3O3/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)/t13-/m0/s1
|
| Chemical Name |
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-6-chloro-4-methyl-3-oxo-1,4-benzoxazine-8-carboxamide
|
| Synonyms |
R-Azasetron; Azasetron, R; 2025360-90-9; 61JC7L0Q4O; UNII-61JC7L0Q4O; ARAZASETRON; N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-6-chloro-4-methyl-3-oxo-1,4-benzoxazine-8-carboxamide; ARAZASETRON [INN];
|
| 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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
