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1mg |
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5mg |
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10mg |
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Purity: ≥98%
A-317567 (A317567) is a novel non-amiloride inhibitor of the acid-sensing ion channel (ASIC) (IC50 = 1.025 μM) with antidepressant and antinociception effects. It acts on three distinct types of native ASIC currents evoked in acutely dissociated adult rat dorsal root ganglion (DRG) neurons. A-317567 produced concentration-dependent inhibition of all pH 4.5-evoked ASIC currents with an IC50 ranging between 2 and 30muM, depending upon the type of ASIC current activated. Unlike amiloride, A-317567 equipotently blocked the sustained phase of ASIC3-like current, a biphasic current akin to cloned ASIC3, which is predominant in DRG. When evaluated in the rat Complete Freud's Adjuvant (CFA)-induced inflammatory thermal hyperalgesia model, A-317567 was fully efficacious at a dose 10-fold lower than amiloride.
ln Vitro |
A-317567 generated concentration-dependent suppression of all pH 4.5-evoked ASIC currents in acutely isolated adult rat dorsal root ganglion (DRG) neurons, with an IC50 spanning from 2 to 30 μM. The sustained phase of the ASIC3-like current, a biphasic current resembling the cloned ASIC3 that predominates in the DRG, is efficiently blocked by A-317567 [2].
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ln Vivo |
In the CFA model, A-317567 (1-100 μmol/kg; ip; once) exhibits complete analgesic action (ED50 = 17 μmol/kg). A-317567 had no discernible impact on contralateral paw withdrawal latency in these circumstances [2].
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Animal Protocol |
Animal/Disease Models: Adult male SD (Sprague-Dawley) rats (230-350 g) injected with Complete Freund's Adjuvant- (CFA-) induced thermal hyperalgesia[2].
Doses: 1-100 μmol/kg Route of Administration: ip; once Experimental Results: demonstrated dose- dependent analgesic effects. |
References |
[1]. Kuduk SD, et al. Synthesis, structure-activity relationship, and pharmacological profile of analogs of the ASIC-3 inhibitor A-317567. ACS Chem Neurosci. 2010 Jan 20;1(1):19-24.
[2]. Dubé GR, et al. Electrophysiological and in vivo characterization of A-317567, a novel blocker of acid sensing ion channels. Pain. 2005 Sep;117(1-2):88-96. |
Molecular Formula |
397.57
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Molecular Weight |
C27H31N3
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CAS # |
371217-32-2
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SMILES |
N=C(C1=CC=C2C=C(C3C(C4=CC5=C(C=C4)CCN(C)C5C(C)C)C3)C=CC2=C1)N
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Synonyms |
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
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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) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.23 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 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.23 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 20.8 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.) |
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.
Evaluation of10b(30 mg/kg) on rat rotarod performance 60 min postdosing.ACS Chem Neurosci.2010 Jan 20;1(1):19-24. th> |
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Evaluation of10band naproxen on mechanical hypersensitivity (left panel) and weight bearing (right panel) in the rat iodoaceate model of osteoarthritis 30 min postdosing: ∗ denotesp< 0.05 (ANOVA).ACS Chem Neurosci.2010 Jan 20;1(1):19-24. td> |
Evaluation of10b(30 mg/kg) on mechanical hypersensitivity in wild-type and ASIC-3 knockout mice in the complete Freund’s adjuvant (CFA) model of inflammatory pain 60 min postdosing.ACS Chem Neurosci.2010 Jan 20;1(1):19-24. td> |