| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
Pozanicline diHCl targets neuronal nicotinic acetylcholine receptors (nAChRs), specifically binding to the α4β2 and α6β2 subtypes. It acts as a partial agonist, meaning it binds to and activates the receptor but with lower efficacy than a full agonist. This selective binding profile is thought to contribute to its therapeutic effects while having a low tendency to cause side effects compared to other drugs in its class.
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| ln Vitro |
ABT-089. Pozanicline is a partial agonist that acts on the α4β2 nAChR. Furthermore, with an EC50 of 0.11 μM, one α6β2 nAChR isoform is extremely sensitive to pozanicline [2]. The nAChR isoforms α6β2 and α4α5β2 are highly selective for pazanicline (ABT-089) [3].
In vitro, Pozanicline diHCl binds to the [³H]cytisine site on nAChRs with a Ki of 16.7 nM. It is a high-affinity and selective partial agonist of the α4β2 nAChR. Its activity is characterized by its ability to partially activate these receptors, leading to a moderate increase in neurotransmitter release. This profile makes it a valuable research tool for studying nAChR function and its role in cognitive disorders. |
| ln Vivo |
Deficits in contextual fear conditioning brought on by nicotine withdrawal are corrected by pozanicline (ABT-089; 0.3 mg/kg and 0.6 mg/kg) [3].
Pozanicline has been evaluated in vivo for the treatment of attention-deficit/hyperactivity disorder (ADHD). Its oral bioavailability and partial agonist profile were designed to provide therapeutic benefit with a reduced side effect profile. The compound has been studied in clinical trials for ADHD, demonstrating its potential as a novel cholinergic agent. Its mechanism involves modulating cholinergic neurotransmission in brain regions involved in attention and cognition. |
| Enzyme Assay |
In vitro receptor binding assays for Pozanicline diHCl involve measuring its affinity for nAChR subtypes. Radioligand binding studies using [³H]cytisine or other nAChR ligands are performed on membranes prepared from cells expressing the α4β2 or other nAChR subtypes. The compound is incubated with increasing concentrations, and its Ki value of 16.7 nM is determined. Selectivity for α4β2 and α6β2 over other subtypes is confirmed.
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| Cell Assay |
For in vitro cell-based assays, cells expressing nAChR subtypes (e.g., α4β2) are cultured and treated with Pozanicline diHCl. Receptor activation is measured by calcium flux assays using fluorescent calcium indicators. Its partial agonist activity is demonstrated by comparing its maximal response to that of a full agonist like nicotine. Its effects on neurotransmitter release can be studied in synaptosomal preparations or neuronal cultures.
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| Animal Protocol |
Animal/Disease Models: 8-12 weeks old adult male C57BL6/J mice [3].
Doses: 0.3 mg/kg and 0.6 mg/kg Route of Administration: Treatment was administered 5 minutes before training and testing contextual fear conditioning Experimental Results: Doses of 0.3 mg/kg and 0.6 mg/kg improved nicotine withdrawal-induced contextual fear conditioning aware of defects. In vivo animal studies with Pozanicline diHCl were conducted in models of ADHD and cognitive impairment. The compound was administered orally to rodents, and its effects on attention, impulsivity, and cognitive performance were assessed using behavioral tests. Its pharmacokinetic profile and brain penetration were also evaluated. The compound advanced to clinical trials, indicating a favorable in vivo profile in preclinical species. |
| ADME/Pharmacokinetics |
Pozanicline diHCl (CAS: 161416-61-1) has a molecular weight of 265.18 g/mol and a molecular formula of C11H18Cl2N2O. It is also known as ABT-089 dihydrochloride. It is an orally bioactive compound and a high-affinity, selective partial agonist of α4β2 nAChR. The compound is soluble in water and is typically stored as a solid at room temperature.
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| Toxicity/Toxicokinetics |
Pozanicline diHCl has been studied in clinical trials for ADHD and was found to have a particularly low tendency to cause side effects compared to other drugs in its class. Common side effects of nAChR agonists can include nausea and gastrointestinal disturbances, but the partial agonist profile of Pozanicline was designed to minimize these. The compound is not currently an FDA-approved drug.
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| References |
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| Additional Infomation |
Pozanicline diHCl (ABT-089 diHCl) is an orally bioactive, subtype-selective neuronal nicotinic acetylcholine receptor (nAChR) partial agonist. It was developed for the treatment of attention-deficit/hyperactivity disorder (ADHD). It has a low tendency to cause side effects. It is not an FDA-approved drug and is intended for research use only.
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| Molecular Formula |
C11H18CL2N2O
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|---|---|
| Molecular Weight |
265.179420948029
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| Exact Mass |
264.079
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| CAS # |
161416-61-1
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| Related CAS # |
Pozanicline;161417-03-4
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| PubChem CID |
23729426
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| Appearance |
White to off-white 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 |
3
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| Heavy Atom Count |
16
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| Complexity |
175
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C(C=CC=N1)OC[C@@H]2CCCN2.Cl.Cl
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| InChi Key |
UGVSESCRKJTJAK-XRIOVQLTSA-N
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| InChi Code |
InChI=1S/C11H16N2O.2ClH/c1-9-11(5-3-6-12-9)14-8-10-4-2-7-13-10;;/h3,5-6,10,13H,2,4,7-8H2,1H3;2*1H/t10-;;/m0../s1
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| Chemical Name |
2-methyl-3-[[(2S)-pyrrolidin-2-yl]methoxy]pyridine;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) |
H2O : ~100 mg/mL (~377.10 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (377.10 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7710 mL | 18.8551 mL | 37.7102 mL | |
| 5 mM | 0.7542 mL | 3.7710 mL | 7.5420 mL | |
| 10 mM | 0.3771 mL | 1.8855 mL | 3.7710 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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