| Size | Price | Stock | Qty |
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| Targets |
Ki: 37 pM (nAChR)[1]
alpha4beta2 neuronal nicotinic acetylcholine receptor. Ki = 37 pM (rat brain) and 55 pM (human alpha4beta2). ~180,000‑fold selective over muscle‑type alpha1beta1deltagamma nAChR. Also binds alpha3beta4 with lower affinity. Negligible affinity for >70 other receptors, enzymes, transporters. |
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| ln Vitro |
Tebanicline is a new and powerful cholinergic nAChR ligand that exhibits preferential selectivity for neuronal nAChRs and analgesic effects. With a Ki of 37 pM, it prevents cytisine from binding to α4β2 neuronal nAChRs. Tebanicline functions as an agonist. ABT-594 has an EC50 value of 140 nM at the transfected human α4β2 neuronal nAChR in K177 cells, with increased 86Rb+ efflux as a measure of cation efflux, and an intrinsic activity compared with (−)-nicotine of 130%; an EC50 value of 340 nM at the nAChR subtype expressed in IMR-32 cells; an EC50 value of 1220 nM at the F11 dorsal root ganglion cell line; and an EC50 value of 56,000 nM measured directly by ion currents at the human α7 homo-oligimeric nAChR produced in oocytes[1].
Full agonist at human alpha4beta2 nAChR (⁸⁶Rb+ efflux, EC50 = 140 nM, intrinsic activity 130% relative to nicotine). EC50 at IMR‑32 cells = 340 nM, at F11 DRG cells = 1220 nM (71% efficacy). At alpha7 nAChR, EC50 = 56,000 nM. At 30 microM, inhibits CGRP release from spinal C‑fibers, contributing to analgesia. |
| ln Vivo |
Tebanicline is a strong antinociceptive drug that works well in models of both acute and chronic pain. Its effects are mostly mediated by activation of central neuronal nAChRs[2]. In mice, tebanicline has strong antinociceptive effects against both acutely painful heat stimulation. Orally administered ABT-594 is active, however it is ten times less effective than it is after intraperitoneal injection. The noncompetitive neuronal nicotinic acetylcholine receptor antagonist ABT-594 blocks the antinociceptive effect but does not reverse it[3]. In rat models of acute thermal pain, persistent chemical pain, and neuropathic pain, temanicol exerts antinociceptive effects. In a heat threshold test, direct tebanicline injection into the nucleus raphe magnus (NRM) is antinociceptive, and the impact of systemic tebanicline is attenuated by the loss of serotonergic neurons in the NRM[4].
Potent antinociception in mouse hot‑plate and rat acute/neuropathic pain models. Orally active but ~10‑fold less potent than i.p. Effects blocked by mecamylamine. Injection into nucleus raphe magnus (NRM) is antinociceptive, and serotonergic lesion attenuates systemic effect, indicating supraspinal serotonergic mechanism. Studied in diabetic peripheral neuropathic pain. |
| Enzyme Assay |
Use rat cortical or hippocampal membranes (0.2‑0.5 mg protein). Incubate with 0.5‑2 nM [3H]‑cytisine and 0.001‑1000 nM tebanicline in 50 mM Tris‑HCl pH 7.4 with 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2 for 60‑90 min at 22degC. Non‑specific: 10 microM (−)‑nicotine. Filter through GF/B (0.5% PEI), wash 3×, count liquid scintillation. Ki = 37 pM.
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| Cell Assay |
Use K177 cells stably expressing human alpha4beta2 nAChR. Seed 50,000/well in 96‑well plates in DMEM/10% FBS/Geneticin/Hygromycin for 48 h. Load with 1 microCi/mL ⁸⁶Rb+ for 60‑90 min at 37degC. Wash, add tebanicline (0.1 nM‑100 microM) for 5 min. Collect supernatant and lyse cells with 1% SDS. Count ⁸⁶Rb+ by scintillation. EC50 = ~140 nM. For patch‑clamp, voltage‑clamp at −70 mV and apply tebanicline rapidly.
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| Animal Protocol |
Hot‑plate test in male ICR mice (20‑30 g, 55degC hot plate, cutoff 30 s). Record baseline latency to hind‑paw lick/jump. Administer tebanicline (0.003‑1 mg/kg i.p. or p.o.) 15‑60 min before test. Calculate %MPE = (post‑latency − baseline)/(cutoff − baseline) × 100. For neuropathic pain, use rat chronic constriction injury (CCI) of sciatic nerve. Administer tebanicline (0.01‑0.3 mg/kg i.p./p.o.) 14 days post‑surgery; assess mechanical allodynia with von Frey filaments.
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| ADME/Pharmacokinetics |
Orally active with ~50‑70% oral bioavailability in rats. Cmax in 0.5‑1 h p.o. 10‑fold lower potency p.o. vs i.p. due to first‑pass metabolism. t½ in rodents ~1‑2 h. Distributes well into CNS. Volume of distribution high. Hepatic metabolism (oxidation, conjugation). No detailed CYP profile fully public.
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| Toxicity/Toxicokinetics |
Significantly improved safety over epibatidine. Therapeutic index much larger. Weak affinity for adrenoreceptors: alpha1B Ki=890 nM, alpha2B=597 nM, alpha2C=342 nM. At >1 microM, potential off‑target interactions. Negligible for 70 other targets. LD50 substantially higher than epibatidine. Not clinically approved. Handle with care as a potent neuroactive compound.
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| References |
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| Additional Infomation |
Potent alpha4beta2 agonist (Ki=37 pM). Analgesic mechanism: activation of central nAChRs at spinal and supraspinal sites (NRM) → modulation of pain signaling → inhibition of CGRP release. Entered clinical trials for diabetic peripheral neuropathic pain. Not FDA/EMA approved. Research tool for nAChR pain pathways and non‑opioid analgesics. CAS 209326‑19‑2. Store at −20degC.
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| Molecular Formula |
C9H13CL3N2O
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|---|---|
| Molecular Weight |
271.57131934166
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| Exact Mass |
270.009
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| CAS # |
209326-19-2
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| Related CAS # |
Tebanicline hydrochloride;203564-54-9
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| PubChem CID |
146673022
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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 |
15
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| Complexity |
168
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1=CC=C(C=N1)OC[C@H]1CCN1.Cl.Cl
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| InChi Key |
HZMFFIXATGBQGR-XCUBXKJBSA-N
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| InChi Code |
InChI=1S/C9H11ClN2O.2ClH/c10-9-2-1-8(5-12-9)13-6-7-3-4-11-7;;/h1-2,5,7,11H,3-4,6H2;2*1H/t7-;;/m1../s1
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| Chemical Name |
5-[[(2R)-azetidin-2-yl]methoxy]-2-chloropyridine;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 (368.23 mM)
DMSO: ≥ 34 mg/mL (125.20 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.66 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 (7.66 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (7.66 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 25 mg/mL (92.06 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6823 mL | 18.4115 mL | 36.8229 mL | |
| 5 mM | 0.7365 mL | 3.6823 mL | 7.3646 mL | |
| 10 mM | 0.3682 mL | 1.8411 mL | 3.6823 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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