| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
5-HT2A Receptor
5-HT2A receptor (agonist, Ki = 0.73 nM for rat; 0.75 nM for human; also reported Ki = 0.26 nM in some studies). It binds with high affinity to 5-HT2C receptors as well (Ki = 0.26 nM for human 5-HT2A; also binds 5-HT2C). |
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| ln Vitro |
The competitive curve generated with the 5-HT1A receptor agonist ipsapirone from [3H]-8-OHDPAT binding sites in both brain areas is significantly shifted to the right by the selective 5-HT2A agonist TCB2 at 30 nM. With TCB2, there is a notable increase in the mean Ki value, indicating a decrease in the 5-HT2A agonist's affinity for the high-affinity 5-HT1A agonist binding sites in both areas. There are also signs that ketanserin may have opposing effects on the hippocampal tissue[2].
In radioligand binding assays, TCB-2 is a high-affinity 5-HT2A receptor agonist, exhibiting Ki values of 0.73 nM and 0.75 nM for rat and human receptors, respectively. It potently stimulates IP3 accumulation in NIH3T3 cells stably expressing rat 5-HT2A receptors, with an EC50 of 36 nM, demonstrating its functional efficacy as a full agonist. |
| ln Vivo |
In C57BL/6J mice, TCB2 (0.5, 1.0, and 2.5 mg/kg) and DOI (0.5, 1.0, 2.5, and 5.0 mg/kg) cause dose-dependent head twitches in comparison to vehicle in an initial dose-response investigation. The amount of head twitches caused by TCB2 and DOI is comparable at all dosages, with the exception that TCB2 causes half as many head twitches as DOI at the highest dose (5.0 mg/kg) (p=0.021). In two distinct experiments, pretreatment with the selective 5-HT2A antagonist MDL 11,939 (1.0 mg/kg) blocked head twitches caused by TCB2 (2.5 mg/kg) and DOI (2.5 mg/kg), confirming that 5-HT2A mediates the head twitch response (p<0.0001). Following TCB2 (5.0 mg/kg, p=0.01; 10.0, p=0.012; with a trend following 2.5 mg/kg, p=0.079) and DOI (10.0 mg/kg, p=0.035), corticosterone levels rise in comparison to vehicle[1].
TCB2 is a potent agonist of the serotonin 5-HT2A receptor. Its selective activation of the 5-HT2A receptor is crucial for mediating various psychological and physiological responses. It is utilized in research exploring the role of 5-HT2A activation in neuropsychiatric disorders and receptor signaling pathways. In rat brain, TCB-2 can shift 5-HT1A agonist ipsapirone binding, indicating crosstalk between these serotonergic systems. It induces head twitch response (HTR) in mice, a classic 5-HT2A-mediated behavioral effect. |
| Enzyme Assay |
Standard radioligand binding assays for 5-HT2A receptors are performed using membrane preparations from rat or human 5-HT2A receptor-expressing cells (e.g., CHO or HEK-293 cells). [3H]-Ketanserin (a selective 5-HT2A antagonist, 1-2 nM) is used as the radioligand. Test compound (TCB2) is incubated with membranes at varying concentrations (10-¹2 to 10-⁶ M) for 60 minutes at 27degC. Nonspecific binding is determined in the presence of 10 uM methysergide or 1 uM ketanserin. Bound radioligand is separated by vacuum filtration through glass fiber filters and counted by liquid scintillation. Ki values (0.73 nM, 0.75 nM) are calculated from competition curves using the Cheng-Prusoff equation. For 5-HT2C receptor binding, [3H]-Mesulergine is used as the radioligand.
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| Cell Assay |
Cell-based functional assays for 5-HT2A agonism are performed using NIH3T3 cells stably expressing rat 5-HT2A receptors or CHO cells expressing human 5-HT2A receptors. The 5-HT2A receptor is Gq-coupled, activating phospholipase C (PLC). For IP accumulation assays, cells are seeded in 24-well plates and labeled with [3H]-myoinositol (1 uCi/well, overnight). After washing, cells are pre-incubated with LiCl (10 mM) for 15 min, then treated with serial dilutions of TCB2 (10-¹2 to 10-⁶ M) for 45-60 min at 37degC. The reaction is terminated by adding ice-cold formic acid or perchloric acid. Total inositol phosphates are separated using anion exchange chromatography (Bio-Rad AG1-X8 resin) and quantified by liquid scintillation counting. EC50 values (e.g., 36 nM) are calculated from concentration-response curves. Alternatively, for higher throughput, IP1 accumulation HTRF assays or calcium flux assays (using Fluo-4 AM and a plate reader) are used as described in the DOI protocol.
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| Animal Protocol |
In vivo animal studies are typically conducted in rodents (male C57BL/6 mice or Sprague-Dawley rats, 8-12 weeks old). TCB-2 is dissolved in saline or a vehicle (e.g., 2% DMSO, 2% Tween 80, 96% saline) and administered intraperitoneally (i.p.) at doses ranging from 0.1 to 5 mg/kg (typical dose 0.3-1.0 mg/kg). The head-twitch response (HTR) in mice is the primary behavioral endpoint. Mice are placed in individual plexiglass cylinders, and head twitches (rapid, paroxysmal rotational movements) are counted for 10-30 minutes post-injection. The number of head twitches is recorded and compared to vehicle-treated controls. To demonstrate receptor specificity, animals can be pretreated with the selective 5-HT2A antagonist M100907 (0.1-1 mg/kg). Pharmacodynamic parameters include total head twitches, latency to first twitch, and duration of response. The maximal response typically occurs within the first 10 minutes. A dose-dependent increase in HTR is observed with TCB-2, and it is often used as a tool to induce a pure 5-HT2A-mediated state without the off-target effects associated with DOI.
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| ADME/Pharmacokinetics |
TCB2 is a research tool, not a therapeutic drug. Comprehensive pharmacokinetic data in animals are not standardized in public literature. As a lipophilic, brain-penetrant small molecule, it is expected to have high oral bioavailability and good brain exposure, typical of serotonergic psychedelics. The plasma half-life is presumed to be short (1-2 hours) in rodents based on the rapid onset and offset of behavioral effects, but specific parameters (Cmax, t1/2, AUC, CL, Vd) are not defined. No formal toxicology studies are available.
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| Toxicity/Toxicokinetics |
In research use, single doses up to 5 mg/kg in mice are tolerated. High doses may produce characteristic serotonergic psychedelic behavioral syndrome. There are no reports of acute organ toxicity in research literature. Owing to its potent and selective 5-HT2A agonist activity, this compound is a controlled substance in many countries and is strictly for research use only.
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| References |
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| Additional Infomation |
TCB2 (TCB-2) is a highly selective 5-HT2A agonist research tool. Compared to the classic agonist DOI, TCB-2 has approximately 10- to 30-fold higher selectivity for the 5-HT2A receptor over the 5-HT2C receptor, making it invaluable for distinguishing 5-HT2A-mediated effects from those mediated by 5-HT2C. It is used in neuropharmacology to study the receptor basis of psychedelic-induced plasticity and in behavioral pharmacology to model psychosis. It is not a clinical drug candidate.
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| Molecular Formula |
C11H15BR2NO2
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|---|---|
| Molecular Weight |
353.05
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| Exact Mass |
350.947
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| CAS # |
912342-28-0
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| Related CAS # |
(R)-TCB2;912342-36-0
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| PubChem CID |
71433791
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| Appearance |
White to off-white solid powder
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| LogP |
3.723
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| Hydrogen Bond Donor Count |
2
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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 |
227
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=CC(=C(C2=C1C(C2)CN)OC)Br.Br
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| InChi Key |
TYMMXVZAUGQKRF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H14BrNO2.BrH/c1-14-9-4-8(12)11(15-2)7-3-6(5-13)10(7)9;/h4,6H,3,5,13H2,1-2H3;1H
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| Chemical Name |
(3-bromo-2,5-dimethoxy-7-bicyclo[4.2.0]octa-1(6),2,4-trienyl)methanamine;hydrobromide
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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: 100 mg/mL (283.25 mM)
H2O: 25 mg/mL (70.81 mM) |
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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 | 2.8325 mL | 14.1623 mL | 28.3246 mL | |
| 5 mM | 0.5665 mL | 2.8325 mL | 5.6649 mL | |
| 10 mM | 0.2832 mL | 1.4162 mL | 2.8325 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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