Tebanicline tosylate targets neuronal nicotinic acetylcholine receptors (nAChRs), particularly the α4β2 subtype in the central nervous system. nAChRs are ligand-gated ion channels that mediate fast synaptic transmission and modulate neurotransmitter release. Tebanicline is a potent agonist of nAChRs with preferential selectivity for neuronal nAChRs. The compound inhibits the binding of cytisine to α4β2 neuronal nAChRs with a Ki of 37 pM, indicating extremely high affinity. Tebanicline was developed as a less toxic analogue of epibatidine, which is some 200 times more potent than morphine as an analgesic but produces extremely dangerous toxic side effects.

Tebanicline tosylate demonstrates potent in vitro activity as a neuronal nAChR agonist. The compound inhibits the binding of cytisine to α4β2 neuronal nAChRs with a Ki of 37 pM. Tebanicline is a novel, potent cholinergic nAChR ligand with analgesic properties that shows preferential selectivity for neuronal nAChRs. The compound's potent nAChR agonism and analgesic properties make it a valuable tool for studying the role of nAChRs in pain perception and for developing non-opioid analgesics. Tebanicline is a potent analgesic with full efficacy in models of acute and persistent pain, and these effects are primarily mediated by an action at central neuronal nAChRs.

ABT-594 , a novel neuronal nicotinic acetylcholine receptor agonist, produced significant antinociceptive effects in mice against both acute noxious thermal stimulation--the hot-plate and cold-plate tests--and persistent visceral irritation--the abdominal constriction (writhing) assay (maximally-effective dose in each test 0.62 micromol/kg, i.p.). . The effect in the hot-plate test peaked at 30 min after i.p. administration and was still present 60 min, but not 120 min, after injection. ABT-594 was orally active, but 10-fold less potent by this route than after i.p. administration. The antinociceptive effect of ABT-594 was prevented, but not reversed, by the noncompetitive neuronal nicotinic acetylcholine receptor antagonist mecamylamine (5 micromol/kg, i.p.). In contrast, the antinociceptive effect of ABT-594 was not prevented by hexamethonium (10 micromol/kg, i.p.), a neuronal nicotinic acetylcholine receptor antagonist that does not readily enter the central nervous system, nor by naltrexone (0.8 micromol/kg), an opioid receptor antagonist. Thus, initiation of antinociception by ABT-594 involves activation of central nicotinic acetylcholine receptors, but does not require activation of naltrexone-sensitive opioid receptors. The antinociceptive effects of morphine and ABT-594 in the mouse hot-plate test appeared to be additive, but ABT-594 did not potentiate the respiratory depression produced by morphine when the two compounds were coadministered. ABT-594 reduced body temperature and spontaneous exploration in the antinociceptive dose range, but did not reliably impair motor coordination in the rotarod test. Thus, it is unlikely that the antinociceptive effects result simply from impaired motor function. The compound also produced an anxiolytic-like effect in the elevated plus maze (at 0.019 and 0.062 micromol/kg, i.p.). Preliminary safety testing revealed an ED50 for overt seizure production of 1.9 micromol/kg, i.p. and an LD50 of 19.1 micromol/kg i.p. in mice, values 10 and 100 times the minimum effective antinociceptive dose of the compound. ABT-594 increased the duration of ethanol-induced hypnotic effects, tended to increase pentobarbital-induced hypnotic effects (P = 0.0502), and had no effect on pentobarbital-induced lethality. These data indicate that ABT-594 is a centrally acting neuronal nicotinic acetylcholine receptor agonist with potent antinociceptive and anxiolytic-like effects in mice.

---

Tebanicline has been evaluated in vivo for its analgesic effects. The compound is a potent analgesic with full efficacy in models of acute and persistent pain, and these effects are primarily mediated by an action at central neuronal nAChRs. Tebanicline is a potent synthetic nicotinic (non-opioid) analgesic drug. The compound's potent analgesic activity and oral effectiveness have been demonstrated in preclinical models. Tebanicline was developed as a less toxic analogue of epibatidine, which is some 200 times more potent than morphine as an analgesic but produces extremely dangerous toxic side effects. Detailed in vivo efficacy data, including specific model results and dosing regimens, are available in the primary literature.

The in vitro receptor binding assay for Tebanicline tosylate measures the compound's binding affinity to α4β2 nAChRs. Membrane preparations from cells expressing human α4β2 nAChRs or rat brain tissue are incubated with varying concentrations of Tebanicline in the presence of a radiolabeled nAChR ligand such as [3H]cytisine or [3H]epibatidine. The amount of bound radioligand is measured by scintillation counting, and Ki values are determined by fitting competition binding curves (Ki = 37 pM for α4β2 nAChRs). The compound is dissolved in DMSO and diluted in assay buffer. Selectivity is assessed by testing the compound against other nAChR subtypes and other receptor targets. Appropriate positive controls and negative controls are included in each assay run.

The in vitro functional assay for Tebanicline tosylate measures the compound's agonist activity at nAChRs. Cells expressing nAChRs or Xenopus oocytes injected with nAChR subunit cRNAs are treated with varying concentrations of Tebanicline or vehicle control. Receptor activation is measured by assessing ion flux (e.g., calcium influx using fluorescent calcium indicators or electrophysiological recordings). The compound's agonist potency and efficacy are determined by fitting dose-response curves. The compound's effects on neurotransmitter release can also be assessed in synaptosome preparations. Tebanicline's preferential selectivity for neuronal nAChRs is confirmed by comparing its activity at neuronal versus muscle-type nAChRs.

In vivo animal experiments with Tebanicline are conducted using rodent models of acute and persistent pain. Tebanicline is administered orally, intraperitoneally, or subcutaneously at various doses. Pain responses are assessed using models such as the hot plate test, tail flick test, formalin test, or neuropathic pain models. The compound's antinociceptive effects are compared to vehicle-treated controls and to reference analgesics such as morphine. The compound's side effect profile, particularly its potential for nicotinic side effects, is also assessed. Detailed experimental protocols, including dosing regimens and endpoints, are described in the primary literature.

Detailed pharmacokinetic (PK) parameters for Tebanicline tosylate are not extensively documented in publicly available sources. The compound is orally effective. Tebanicline tosylate has a molecular weight of 370.85 and a chemical formula of C16H19ClN2O4S. The compound is soluble in DMSO for formulation purposes. For in vivo oral administration, Tebanicline is typically formulated using appropriate vehicles to ensure adequate solubility and stability. The compound should be stored under conditions recommended by the manufacturer to maintain stability and prevent degradation. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are available in the primary literature and should be consulted for specific experimental planning.

Comprehensive toxicological data for Tebanicline tosylate are not extensively documented in publicly available sources. As a research-grade compound, Tebanicline tosylate is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. Tebanicline was developed as a less toxic analogue of epibatidine, but appropriate safety precautions should still be taken. Comprehensive toxicological profiling is not available from the current search results.

J Physiol Paris. 1998 Jun-Aug;92(3-4):221-4.;Eur J Pharmacol. 1998 Apr 3;346(1):23-33.

Tebanicline tosylate is a research compound developed for studying the role of neuronal nAChRs in pain perception and for evaluating non-opioid analgesics. The compound is also known as ABT-594. Tebanicline is a potent synthetic nicotinic (non-opioid) analgesic drug developed as a less toxic analogue of epibatidine. Tebanicline inhibits the binding of cytisine to α4β2 neuronal nAChRs with a Ki of 37 pM. The compound is a potent analgesic with full efficacy in models of acute and persistent pain. Tebanicline is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical pain research. Tebanicline tosylate is available from various chemical suppliers for research purposes.

C9H11N2OCL.C7H8O3S

370.85106

370.075

198283-74-8

203564-54-9 (HCl);209326-19-2 (2HCl);198283-73-7;198283-74-8; 209326-18-1 (benzoate);

9907432

Typically exists as solid at room temperature

2

6

4

24

374

1

CC1=CC=C(C=C1)S(=O)(=O)O.C1CNC1COC2=CN=C(C=C2)Cl

JCPWIGCGJUGLJQ-OGFXRTJISA-N

InChI=1S/C9H11ClN2O.C7H8O3S/c10-9-2-1-8(5-12-9)13-6-7-3-4-11-7;1-6-2-4-7(5-3-6)11(8,9)10/h1-2,5,7,11H,3-4,6H2;2-5H,1H3,(H,8,9,10)/t7-;/m1./s1

Pyridine, 5-((2R)-2-azetidinylmethoxy)-2-chloro-, mono(4-methylbenzenesulfonate)

ABT-594 tosylate; ABT 594; ABT594; Ebanicline tosylate.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

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 Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

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
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)