| Size | Price | Stock | Qty |
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| 250mg |
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| 500mg |
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| Other Sizes |
| Targets |
(E)-3,4,5-Trimethoxycinnamic acid targets GABAA/Benzodiazepine (BZ) receptors as a potent agonist. It also exhibits good binding affinity to 5-HT2C and 5-HT1A serotonin receptors, with IC50 values of 2.5 and 7.6 μM, respectively. Activation of GABAA/BZ receptors enhances inhibitory neurotransmission, which contributes to the compound's anticonvulsant and sedative effects. The compound's binding to serotonin receptors may contribute to its additional pharmacological effects. In cerebellar granule cells, TMCA enhances the expression of GAD65 (glutamic acid decarboxylase) and the GABAA receptor γ subunit. This upregulation of GABAergic components may further enhance inhibitory neurotransmission. The compound also increases chloride influx in response to activation.
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| ln Vitro |
In cerebellar granule cells, (E)-3,4,5-Trimethoxycinnamic Acid (10 μg/mL, 1 h) enhances the expression of GAD65 and GABAA receptor γ subunit [3]. Cl-influx significantly increased in response to (E)-3,4,5-Trimethoxycinnamic acid (0–10 μg/mL, 1 h) [3].
In vitro studies have demonstrated that (E)-3,4,5-Trimethoxycinnamic acid enhances the expression of GAD65 and the GABAA receptor γ subunit in cerebellar granule cells at a concentration of 10 μg/mL for 1 hour. The compound also significantly increases chloride influx at concentrations of 1-10 μg/mL. TMCA shows good binding affinity to 5-HT2C and 5-HT1A receptors with IC50 values of 2.5 and 7.6 μM, respectively. These in vitro findings support the compound's role as a GABAA/BZ receptor agonist and its potential anticonvulsant and sedative activities. The compound's effects on GAD65 and GABA receptor expression suggest a mechanism that may enhance GABAergic neurotransmission. TMCA may be utilized in the study of insomnia, headache, and epilepsy. |
| ln Vivo |
(E)-3,4,5-Trimethoxycinnamic acid (0–20 mg/kg IP once) exhibits antiepileptic properties [2]. (E)-3,4,5-Trimethoxycinnamic Acid (0–10 mg/kg, orally administered once) can increase the hypnotizing effect in mice administered pentobarbital [3].
In vivo, (E)-3,4,5-Trimethoxycinnamic acid demonstrates anticonvulsant properties in animal models. In adult male Kunming mice subjected to maximum electroshock (MES), the compound at doses of 10 and 20 mg/kg (intraperitoneal administration) dramatically reduced the incidence of tetanic hindlimb extension (THE) to 50% and 20% of vehicle control values. In a pentylenetetrazole (PTZ) seizure model, TMCA significantly delayed the onset of myoclonic jerks and reduced seizure severity. The compound also increases the hypnotizing effect in mice administered pentobarbital when given orally at 0-10 mg/kg. These findings support the compound's anticonvulsant and sedative activities. TMCA is orally active and may be studied for the treatment of epilepsy, insomnia, and headache. |
| Enzyme Assay |
In vitro receptor binding assays for (E)-3,4,5-Trimethoxycinnamic acid typically involve radioligand binding studies using membrane preparations from cells expressing GABAA/BZ receptors or serotonin receptors (5-HT2C and 5-HT1A). The compound is dissolved in DMSO and diluted in assay buffer to concentrations ranging from 0.1-100 μM. Membrane preparations are incubated with radiolabeled ligands (e.g., [3H]flunitrazepam for GABAA/BZ or [3H]LSD for serotonin receptors) and varying concentrations of TMCA. Non-specific binding is determined using excess unlabeled ligand. IC50 values are calculated by plotting the percentage of specific binding inhibition against the compound concentration. The compound shows good binding affinity to 5-HT2C (IC50 = 2.5 μM) and 5-HT1A (IC50 = 7.6 μM) receptors.
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| Cell Assay |
Western Blot analysis [3]
Cell Types: primary cultured cerebellar granule cells Tested Concentrations: 10 μg/mL Incubation Duration: 1 h Experimental Results: The expression of GAD65 (glutamic acid decarboxylase) and GABAA receptor γ subunit increased, but not Affects the content of a and b subunits in GABAA receptors. Cell viability assay [3] Cell Types: Primary cultured cerebellar granule cells Tested Concentrations: 1, 3, 5, 10 μg/mL Incubation Duration: 1 hour Experimental Results: Cl- influx increased Dramatically. In vitro cell-based assays using (E)-3,4,5-Trimethoxycinnamic acid are conducted in primary cultured cerebellar granule cells. Cells are treated with TMCA at concentrations of 1-10 μg/mL for 1 hour. After treatment, cells are harvested for Western blot analysis to measure the expression of GAD65 and GABAA receptor subunits. Chloride influx is measured using a fluorescent indicator such as SPQ or MQAE. Cell viability is assessed using standard assays such as MTT. The compound significantly enhances GAD65 and GABAA receptor γ subunit expression at 10 μg/mL. Chloride influx is significantly increased in response to TMCA at 1-10 μg/mL. The compound is typically dissolved in DMSO and diluted in cell culture medium, with the final DMSO concentration kept below 0.1%. |
| Animal Protocol |
Animal/Disease Models: Adult male Kunming mice (18-20 g, maximum electroshock (MES) and pentylenetetrazole (PTZ) models) [2]
Doses: 5, 10 and 20 mg/kg; 10 mL/kg Route of Administration: IP, primary Experimental Results: The incidence of MES-induced THE (tetanic hindlimb extension) was Dramatically diminished to 50% and 20% of vehicle control values at 10 and 20 mg/kg. At the 5 mg/kg dose, the incidence of MES-induced THE was only diminished by 80%. In a PTZ seizure model, the onset of myoclonic jerks (MJ) was Dramatically delayed and seizure severity and mortality were diminished compared with vehicle-treated animals. The incidence of generalized clonic convulsions (stage 4) disappeared at both 10 and 20 mg/kg doses. Animal/Disease Models: ICR male mice (25-28 g, 10-12 per group) [3] Doses: 2, 5 and 10 mg/kg Route of Administration: oral (po), once, 15 minutes and 1 before injection hour, results of pentobarbital injection: significant decrease in locomotor activity at 10 mg/kg. NREM and total sleep time increased, but wakefulness decreas In vivo animal experiments with (E)-3,4,5-Trimethoxycinnamic acid are conducted in adult male Kunming mice (18-20 g) using maximum electroshock (MES) and pentylenetetrazole (PTZ) seizure models. For MES studies, TMCA is administered intraperitoneally at doses of 5, 10, and 20 mg/kg (10 mL/kg). The incidence of tetanic hindlimb extension (THE) is monitored. For PTZ studies, the onset of myoclonic jerks and seizure severity are recorded. For hypnotic effect studies, TMCA is administered orally at 0-10 mg/kg to mice given pentobarbital, and sleeping time is measured. The compound demonstrates dose-dependent anticonvulsant effects, with 10 and 20 mg/kg doses reducing THE incidence to 50% and 20% of control values, respectively. In PTZ models, TMCA significantly delays myoclonic jerk onset. |
| ADME/Pharmacokinetics |
(E)-3,4,5-Trimethoxycinnamic acid is orally active with good bioavailability. In animal studies, the compound is administered intraperitoneally at doses of 5-20 mg/kg or orally at 0-10 mg/kg. The compound is absorbed and reaches the brain where it acts on GABAA/BZ receptors. The compound has a molecular weight of 238.24 g/mol and is a solid at room temperature. For long-term storage, the compound should be kept at room temperature in a cool, dark place (<15°C). Pharmacokinetic studies in animals would typically measure plasma concentrations of TMCA over time to determine Cmax, Tmax, half-life, and bioavailability. The compound's oral activity makes it suitable for studies requiring oral administration.
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| Toxicity/Toxicokinetics |
The toxicity of (E)-3,4,5-Trimethoxycinnamic acid has been evaluated in animal studies. At therapeutic doses (5-20 mg/kg), the compound is generally well-tolerated with no significant adverse effects reported. The compound is a natural product isolated from Polygala tenuifolia Willd, which has a history of traditional use. In animal models, the compound demonstrates anticonvulsant and sedative activities without significant toxicity at the doses tested. The compound is intended for research use only and is not for human use. Standard laboratory safety precautions should be followed when handling the compound. The compound is not classified as a highly toxic substance. Safety data sheets recommend standard handling procedures for research chemicals.
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| References |
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| Additional Infomation |
3,4,5-Trimethoxycinnamic acid is a methoxycinnamic acid in which the 3, 4, and 5 positions are each replaced by three methoxy groups. It is an allergen. It is the conjugate acid of 3,4,5-trimethoxycinnamic acid ester. It has been reported to be found in Polygala tenuifolia, Piper swartzianum, and Piper tuberculatum, and relevant data are available.
(E)-3,4,5-Trimethoxycinnamic acid (CAS 20329-98-0) is a polymethoxy-substituted cinnamic acid and an orally active, potent GABAA/BZ receptor agonist. It has the molecular formula C12H14O5 and a molecular weight of 238.24 g/mol. The compound exhibits good binding affinity to 5-HT2C and 5-HT1A receptors with IC50 values of 2.5 and 7.6 μM, respectively. It has anticonvulsant and sedative activities and may be studied for insomnia, headache, and epilepsy. The compound is a phenylpropanoid isolated from the roots of Polygala tenuifolia Willd, with anti-stress effects, prolonging sleeping time in animals. The trans isomer is the biologically active form. The compound is stored at room temperature in a cool, dark place (<15°C). It is also known as 3,4,5-Trimethoxy-trans-cinnamic acid. |
| Molecular Formula |
C12H14O5
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|---|---|
| Molecular Weight |
238.2366
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| Exact Mass |
238.084
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| CAS # |
20329-98-0
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| PubChem CID |
735755
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
396.4±37.0 °C at 760 mmHg
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| Melting Point |
125-127ºC(lit.)
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| Flash Point |
151.5±20.0 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.560
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| LogP |
2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
17
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| Complexity |
262
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=CC(=CC(=C1OC)OC)/C=C/C(=O)O
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| InChi Key |
YTFVRYKNXDADBI-SNAWJCMRSA-N
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| InChi Code |
InChI=1S/C12H14O5/c1-15-9-6-8(4-5-11(13)14)7-10(16-2)12(9)17-3/h4-7H,1-3H3,(H,13,14)/b5-4+
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| Chemical Name |
(E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoic acid
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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 |
| 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 (~419.74 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.49 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 (10.49 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 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (10.49 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.1974 mL | 20.9872 mL | 41.9745 mL | |
| 5 mM | 0.8395 mL | 4.1974 mL | 8.3949 mL | |
| 10 mM | 0.4197 mL | 2.0987 mL | 4.1974 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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