| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
Purity: ≥98%
AZD-6280 is a novel, potent and selective GABAA(α2/3) receptor modulator, used for treatment of generalized anxiety disorder. Following administration of AZD6280 at 10 mg and 40 mg doses, prolactin levels increased significantly compared with placebo (difference 42.0%, 19.8%, and 32.8%, respectively), suggesting that the α2 and/or α3 receptor subtypes are involved in GABAergic modulation of prolactin secretion, although possible roles of the α1 and α5 receptor subtypes are not excluded. The increases in prolactin levels after administration of AZD7325 at 2 mg and 10 mg doses (difference 7.6% and 10.5%, respectively) did not reach statistical significance, suggesting that doses of AZD7325 or intrinsic efficacy at the α2 and α3 receptor subtypes may have been too low.
| ln Vivo |
In a double-blind, placebo-controlled, randomized, crossover study involving healthy male volunteers, single oral doses of AZD6280 significantly increased plasma prolactin levels in a dose-dependent manner compared to placebo. Administration of a 10 mg dose resulted in a 19.8% increase (95% CI: 8.2% to 32.6%, P = 0.0007). Administration of a 40 mg dose resulted in a larger increase of 32.8% (95% CI: 20.0% to 47.0%, P < 0.0001). The increase suggests that modulation of α₂ and/or α₃ GABAA receptor subtypes is involved in the GABAergic control of the tuberoinfundibular dopaminergic pathway, which tonically inhibits prolactin secretion.[1]
The prolactin increase observed after a 40 mg dose of AZD6280 was not statistically significantly different from the 42.0% increase observed after a 2 mg dose of the non-selective benzodiazepine lorazepam.[1] |
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| ADME/Pharmacokinetics |
This article notes that the prolactin study is part of a larger Phase I pharmacokinetic and pharmacodynamic study of AZD6280. However, specific pharmacokinetic parameters of AZD6280 (e.g., absorption, distribution, metabolism, excretion, half-life, oral bioavailability) are not reported in this article. Complete pharmacokinetic results have been reported in other literature. [1]
The drug is administered in a single oral dose. Subjects fasted for at least 2.5 hours after taking a small standard breakfast until administration (usually between 11:00 AM and 12:00 PM), and continued to fast for 4 hours after administration. [1] |
| References | |
| Additional Infomation |
AZD6280 has been used in studies of the basic science of anxiety disorders.
AZD6280 is a novel partial α₂/α₃ subunit selective GABAA receptor modulator. Such compounds are thought to have anxiolytic effects and sedative effects that may be weaker than non-selective benzodiazepines, and may have potential value in the treatment of diseases such as schizophrenia due to their differential effects on dopaminergic circuits. [1] This study aimed to evaluate the effect of selective GABAA receptor modulators on prolactin secretion as an indirect indicator of the activity of the dopaminergic pathway in the tuberous infundibulum of humans. [1] Results showed that AZD6280 increased prolactin levels in healthy men, supporting the role of α₂/α₃ subunit-containing GABAA receptors in regulating this neuroendocrine pathway in vivo. [1] AZD6280 had a more significant effect on prolactin than another α₂/α₃ subunit modulator, AZD7325, tested in the same study, which may be related to differences in dosage or mechanism of action. Intrinsic efficacy. [1] |
| Molecular Formula |
C20H22N4O3
|
|---|---|
| Molecular Weight |
366.4137
|
| Exact Mass |
366.169
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| CAS # |
942436-93-3
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| PubChem CID |
23630026
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.192
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
|
| Heavy Atom Count |
27
|
| Complexity |
492
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
NVWCZRPXYVDQEE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H22N4O3/c1-4-10-22-20(25)19-17(21)14-7-5-6-13(18(14)23-24-19)15-11-12(26-2)8-9-16(15)27-3/h5-9,11H,4,10H2,1-3H3,(H2,21,23)(H,22,25)
|
| Chemical Name |
4-amino-8-(2,5-dimethoxyphenyl)-N-propylcinnoline-3-carboxamide
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~62.5 mg/mL (~170.57 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.68 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7292 mL | 13.6459 mL | 27.2918 mL | |
| 5 mM | 0.5458 mL | 2.7292 mL | 5.4584 mL | |
| 10 mM | 0.2729 mL | 1.3646 mL | 2.7292 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.
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.
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