1. Membrane Transporter/Ion Channel Neuronal Signaling GPCR/G Protein
  2. GABA Receptor 5-HT Receptor
  3. (E)-3,4,5-Trimethoxycinnamic acid

(E)-3,4,5-Trimethoxycinnamic acid  (Synonyms: TMCA)

Cat. No.: HY-W050162 Purity: 99.95%
SDS COA Handling Instructions

(E)-3,4,5-Trimethoxycinnamic acid (TMCA) is a cinnamic acid substituted by multi-methoxy groups. (E)-3,4,5-Trimethoxycinnamic acid is an orally active and potent GABAA/BZ receptor agonist. (E)-3,4,5-Trimethoxycinnamic exhibits favourable binding affinity to 5-HT2C and 5-HT1A receptor, with IC50 values of 2.5 and 7.6 μM, respectively. (E)-3,4,5-Trimethoxycinnamic acid shows anticonvulsant and sedative activity. (E)-3,4,5-Trimethoxycinnamic acid can be used for the research of insomnia, headache and epilepsy.

For research use only. We do not sell to patients.

(E)-3,4,5-Trimethoxycinnamic acid Chemical Structure

(E)-3,4,5-Trimethoxycinnamic acid Chemical Structure

CAS No. : 20329-98-0

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Based on 1 publication(s) in Google Scholar

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  • Purity & Documentation

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Description

(E)-3,4,5-Trimethoxycinnamic acid (TMCA) is a cinnamic acid substituted by multi-methoxy groups. (E)-3,4,5-Trimethoxycinnamic acid is an orally active and potent GABAA/BZ receptor agonist. (E)-3,4,5-Trimethoxycinnamic exhibits favourable binding affinity to 5-HT2C and 5-HT1A receptor, with IC50 values of 2.5 and 7.6 μM, respectively. (E)-3,4,5-Trimethoxycinnamic acid shows anticonvulsant and sedative activity. (E)-3,4,5-Trimethoxycinnamic acid can be used for the research of insomnia, headache and epilepsy[1][2][3].

IC50 & Target

5-HT1A Receptor

7.6 μM (IC50)

5-HT2C Receptor

2.5 μM (IC50)

5-HT2A Receptor

>10 μM (IC50)

5-HT6 Receptor

>10 μM (IC50)

5-HT7 Receptor

>10 μM (IC50)

In Vitro

(E)-3,4,5-Trimethoxycinnamic acid (10 μg/mL, 1 h) increases the expressions of GAD65 and γ-subunit of GABAA receptors in the cerebellar granule cells[3].
(E)-3,4,5-Trimethoxycinnamic acid (0-10 μg/mL, 1 h) shows a significant increase in Cl- influx[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis[3]

Cell Line: Primary cultured cerebellar granule cells
Concentration: 10 μg/mL
Incubation Time: 1 h
Result: Increased expression of GAD65 (glutamic acid decarboxylase) and γ-subunit of GABAA receptors, but did not influence the amounts of a-, b-subunits in the GABAA receptors.

Cell Viability Assay[3]

Cell Line: Primary cultured cerebellar granule cells
Concentration: 1, 3, 5, 10 μg/mL
Incubation Time: 1 h
Result: Produced a significant increase in Cl- influx.
In Vivo

(E)-3,4,5-Trimethoxycinnamic acid (0-20 mg/kg, IP, once) shows anti-seizure effects[2].
(E)-3,4,5-Trimethoxycinnamic acid (0-10 mg/kg, Orally, once) enhances hypnotic effects in pentobarbital-treated mice[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Ault male KunMing-strain mice (18-20 g, maximal electroshock (MES) and pentylenetetrazol (PTZ) models)[2]
Dosage: 5, 10 and 20 mg/kg; 10 mL/kg
Administration: IP, once
Result: Significantly decreased the incidence of MES-induced THE (tonic hindlimb extension) to 50% and 20% of the value of the vehicle controls at 10 and 20 mg/kg. Decreased the incidence of MES-induced THE to only 80% at 5 mg/kg. Significantly delayed the onset of myoclonic jerks (MJ), and decreased the seizure severity and mortality compared with the vehicle-treated animals in PTZ seizure model. The incidence of generalized clonic convulsions (stage 4) disappeared at doses of both 10 and 20 mg/kg.
Animal Model: ICR male mice (25-28 g, 10-12 in each group)[3]
Dosage: 2, 5 and 10 mg/kg
Administration: Orally (p.o.), once, 15 min and 1 h prior to pentobarbital injection
Result: Significantly decreased locomotor activity at 10 mg/kg. Increased NREM and total sleep, but decreased wakefulness.
Clinical Trial
Molecular Weight

238.24

Formula

C12H14O5

CAS No.
Appearance

Solid

Color

White to off-white

SMILES

O=C(O)/C=C/C1=CC(OC)=C(OC)C(OC)=C1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (419.74 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 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
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
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Concentration
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Volume
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Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

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Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (10.49 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.5 mg/mL (10.49 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.95%

References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 4.1974 mL 20.9872 mL 41.9745 mL 104.9362 mL
5 mM 0.8395 mL 4.1974 mL 8.3949 mL 20.9872 mL
10 mM 0.4197 mL 2.0987 mL 4.1974 mL 10.4936 mL
15 mM 0.2798 mL 1.3991 mL 2.7983 mL 6.9957 mL
20 mM 0.2099 mL 1.0494 mL 2.0987 mL 5.2468 mL
25 mM 0.1679 mL 0.8395 mL 1.6790 mL 4.1974 mL
30 mM 0.1399 mL 0.6996 mL 1.3991 mL 3.4979 mL
40 mM 0.1049 mL 0.5247 mL 1.0494 mL 2.6234 mL
50 mM 0.0839 mL 0.4197 mL 0.8395 mL 2.0987 mL
60 mM 0.0700 mL 0.3498 mL 0.6996 mL 1.7489 mL
80 mM 0.0525 mL 0.2623 mL 0.5247 mL 1.3117 mL
100 mM 0.0420 mL 0.2099 mL 0.4197 mL 1.0494 mL
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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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(E)-3,4,5-Trimethoxycinnamic acid
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