| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
The primary target of A-412997 dihydrochloride is the dopamine D4 receptor (D4R). It acts as a potent and full agonist. It has high affinity and selectivity for the D4 subtype, with Ki values of 7.9 nM (human D4) and 12.1 nM (rat D4). It displays no affinity for other dopamine receptor subtypes (Ki > 1 microM).
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| ln Vitro |
In vitro, A-412997 is a full agonist at rat dopamine D4 receptors in a calcium flux functional assay, with an EC50 of 28.4 nM and an intrinsic activity of 0.83. It has Ki values of 7.9 nM and 12.1 nM for human and rat D4 receptors, respectively. It shows no significant activity at D2-like receptors, making it a highly selective tool.
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| ln Vivo |
In vivo, A-412997 (0.1 umol/kg, s.c.) induces penile erection in a conscious rat model, an effect linked to D4 receptor activation. It also has wake-promoting, antipsychotic-like, and cognitive-enhancing properties in rodent models. In a neurodevelopmental model of schizophrenia, it enhances gamma activity, a biomarker of cognitive function.
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| Enzyme Assay |
The non-cellular binding assay uses membranes from cells expressing the human dopamine D4 receptor. Membranes are incubated with a radioligand like [3H]spiperone or [3H]nemonapride and increasing concentrations of A-412997 in 50 mM Tris-HCl, pH 7.4, at 25degC for 60 min. Nonspecific binding is defined with 10 uM haloperidol. For functional assays, intracellular calcium flux (a surrogate for G protein activation) is measured. Cells expressing D4 and a chimeric G-protein are loaded with a calcium-sensitive dye (e.g., Fluo-4). Varying concentrations of A-412997 are added, and fluorescence is read on a plate reader to calculate EC50.
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| Animal Protocol |
An in vivo protocol for studying cognitive effects uses the novel object recognition task in rats. A-412997 (0.3-3 mg/kg, sc) is administered immediately after the training phase. The retention test is performed 24 hours later. An increase in discrimination index in treated rats compared to vehicle controls indicates D4 agonist-mediated enhancement of long-term memory consolidation.
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| ADME/Pharmacokinetics |
No specific PK data for A-412997 is provided, but it is reported to display high oral bioavailability and a superior selectivity profile, indicating it is well-absorbed. It is active in vivo via subcutaneous and oral routes in rodents, suggesting favorable ADME properties that allow it to reach its CNS targets.
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| Toxicity/Toxicokinetics |
No detailed toxicology data is provided, but the compound is well-tolerated at active doses in animal studies. At high doses (e.g., 10 mg/kg, sc), it may produce behavioral effects, but the therapeutic window for its wake-promoting or cognitive effects is generally separated from overt toxicity or motor side effects.
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| References |
[1]. Browman KE, et al. A-412997, a selective dopamine D4 agonist, improves cognitive performance in rats. Pharmacol Biochem Behav. 2005 Sep;82(1):148-55.
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| Additional Infomation |
A-412997 is one of the most selective D4 agonists available, with over 1,000-fold selectivity for D4 over other dopamine receptors. This high selectivity is critical because it allows researchers to attribute biological effects (such as wakefulness, penile erection, or cognitive enhancement) specifically to D4 receptor activation without the confounding effects of D2 or D3 receptor engagement, which can cause motor or hormonal side effects.
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| Molecular Formula |
C19H25CL2N3O
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|---|---|
| Molecular Weight |
382.33
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| Exact Mass |
381.137
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| CAS # |
1347744-96-0
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| PubChem CID |
90488953
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
379
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.Cl.CC1C=CC=C(NC(CN2CCC(C3=CC=CC=N3)CC2)=O)C=1
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| InChi Key |
KIGNSSHMCNBHQX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H23N3O.2ClH/c1-15-5-4-6-17(13-15)21-19(23)14-22-11-8-16(9-12-22)18-7-2-3-10-20-18;;/h2-7,10,13,16H,8-9,11-12,14H2,1H3,(H,21,23);2*1H
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| Chemical Name |
N-(3-methylphenyl)-2-(4-pyridin-2-ylpiperidin-1-yl)acetamide;dihydrochloride
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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) |
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
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| 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6155 mL | 13.0777 mL | 26.1554 mL | |
| 5 mM | 0.5231 mL | 2.6155 mL | 5.2311 mL | |
| 10 mM | 0.2616 mL | 1.3078 mL | 2.6155 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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