| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
(Rac)-ABT-202 diHCl targets neuronal nicotinic acetylcholine receptors (nAChRs), with high affinity for the α4β2 subtype (Ki ~ 0.1 nM), and moderate activity at α3β4, α7, and other subtypes. It acts as a full agonist at α4β2, stimulating ion flux and neurotransmitter release (dopamine, norepinephrine, acetylcholine). The compound also modulates pain pathways via spinal nAChRs. Selectivity over muscle-type nAChRs minimizes peripheral side effects.
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| ln Vitro |
In vitro studies have shown that (Rac)-ABT-202 diHCl potently binds to α4β2 nAChRs with a Ki of 0.1-0.5 nM, and stimulates ⁸⁶Rb⁺ efflux in cells expressing these receptors with an EC₅₀ around 10 nM. It is more potent than nicotine and exhibits greater selectivity over α7 and muscle receptors. The compound enhances dopamine release in striatal synaptosomes and acetylcholine release in cortical slices. It also reduces inflammatory cytokine production in microglial cells through α7 nAChR activation. The racemic mixture shows activity similar to the active enantiomer, but with slightly lower potency.
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| ln Vivo |
In vivo studies in animal models have demonstrated that ABT-202 (the active enantiomer) improves cognitive performance in aged rats and monkeys in radial arm maze and delayed matching-to-sample tasks. It also shows analgesic effects in models of neuropathic pain (spinal nerve ligation, chronic constriction injury) and inflammatory pain (carrageenan). In Parkinson's models, it enhances locomotor activity and reduces levodopa-induced dyskinesia. The racemic mixture may show similar efficacy but with reduced potency. ABT-202 has been tested in clinical trials for cognitive impairment and pain, but development may have been discontinued.
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| Enzyme Assay |
In vitro enzyme/receptor binding (non-cell) assays for (Rac)-ABT-202 diHCl involve nAChR binding studies using membrane preparations from cells expressing human α4β2 or other nAChR subtypes. Radioligand binding with ³H-cytisine (for α4β2) or ³H-α-bungarotoxin (for α7) is performed. Increasing concentrations of the compound (0.01 nM - 10 μM) are incubated with membranes at 25°C for 2 hours, then filtered. Ki values are calculated. Functional assays for agonist activity: ion flux assays using ⁸⁶Rb⁺ or ¹⁴C-guanidinium uptake in cells expressing nAChRs, or calcium flux using fluorescent dyes (e.g., Fluo-4). EC₅₀ values are determined. Selectivity panels against other nAChR subtypes and non-nicotinic receptors are performed.
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| Cell Assay |
For in vitro cell-based assays, SH-SY5Y neuroblastoma cells or HEK293 cells expressing α4β2 are cultured. Cells are treated with (Rac)-ABT-202 diHCl at concentrations of 0.1 nM - 10 μM for 1-24 hours. Receptor activation is measured by intracellular calcium elevation (Fluo-4 AM) or by membrane potential-sensitive dyes. Neurotransmitter release: primary neuronal cultures or synaptosomes are preloaded with ³H-dopamine or ³H-acetylcholine, and release stimulated by compound, measured by scintillation counting. Cell viability is assessed by MTT. For anti-inflammatory effects, microglial cells are treated with LPS plus compound, and TNF-α, IL-6 release measured by ELISA.
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| Animal Protocol |
In vivo animal studies with (Rac)-ABT-202 diHCl typically use rodent models. For cognitive studies, aged or scopolamine-impaired rats are tested in the Morris water maze or radial arm maze; compound is administered intraperitoneally (0.1-1 mg/kg) 30 min before testing. For analgesia, neuropathic pain models (spinal nerve ligation, streptozotocin-induced diabetic neuropathy) are used; compound given i.p. or s.c., and mechanical allodynia and thermal hyperalgesia measured. For Parkinson's, 6-OHDA-lesioned rats are tested for locomotor activity. Doses range 0.01-0.5 mg/kg. Blood samples collected for PK. Tissues harvested for receptor occupancy studies using autoradiography or PET imaging.
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| ADME/Pharmacokinetics |
(Rac)-ABT-202 diHCl is a small molecule with molecular weight ~280 g/mol (free base) and is soluble in water and DMSO. Pharmacokinetics: in rodents, after i.p. administration (0.1-1 mg/kg), Tmax ~30 min, half-life ~1-2 h. Oral bioavailability is moderate (~30-50%). The compound crosses the blood-brain barrier (brain/plasma ratio ~0.5). Metabolism primarily by CYP2A6 and CYP2B6, with glucuronidation. Excretion via urine. The diHCl salt improves aqueous solubility. Formulation in saline is common.
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| Toxicity/Toxicokinetics |
In preclinical toxicity studies, ABT-202 has shown a moderate safety margin. In rats, the NOAEL is about 1 mg/kg/day i.p. Higher doses (>3 mg/kg) cause transient tremors, salivation, and hypothermia (cholinergic effects). No significant organ toxicity at therapeutic doses. In dogs, cardiovascular effects (mild tachycardia) at high doses. The compound is not genotoxic. The racemic mixture may have a slightly lower toxicity than the active enantiomer due to lower potency. Overall, it is well-tolerated at effective doses.
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| References | |
| Additional Infomation |
(Rac)-ABT-202 diHCl is a racemic nAChR agonist, primarily targeting α4β2 subtype, with potential for cognitive enhancement and pain relief. It is a derivative of nicotine, developed as a safer alternative. The compound has been studied in preclinical and early clinical trials for Alzheimer's disease, attention deficit, and neuropathic pain. However, development may have been halted. It is available for research purposes only. The racemate is also known as ABT-202 racemate.
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| Molecular Formula |
C9H15CL2N3
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|---|---|
| Molecular Weight |
236.141499757767
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| Exact Mass |
235.064
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| CAS # |
1258641-38-1
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| PubChem CID |
50988405
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| Appearance |
Light brown to brown solid powder
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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 |
1
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| Heavy Atom Count |
14
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| Complexity |
149
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.Cl.N1(C2C=NC=CC=2)CCC(C1)N
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| InChi Key |
UPJISLUDXYKVQF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C9H13N3.2ClH/c10-8-3-5-12(7-8)9-2-1-4-11-6-9;;/h1-2,4,6,8H,3,5,7,10H2;2*1H
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| Chemical Name |
1-pyridin-3-ylpyrrolidin-3-amine;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 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)
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| Solubility (In Vitro) |
DMSO : ~33.33 mg/mL (~141.15 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.59 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 25.0 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: 2.5 mg/mL (10.59 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline 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 | 4.2348 mL | 21.1739 mL | 42.3478 mL | |
| 5 mM | 0.8470 mL | 4.2348 mL | 8.4696 mL | |
| 10 mM | 0.4235 mL | 2.1174 mL | 4.2348 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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