| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
| Targets |
1. 5-HT1C receptors [1]
2. Human serotonin transporter (SERT, Ki = 14.6 nM), norepinephrine transporter (NET, Ki = 2.3 nM), dopamine transporter (DAT, Ki = 101 nM), organic cation transporter 1 (OCT1, Ki = 1.1 μM), organic cation transporter 2 (OCT2, Ki = 0.4 μM), organic cation transporter 3 (OCT3, Ki = 0.9 μM) [2] 3. Dopamine D2 receptors, 5-HT2 receptors, tryptamine binding sites [3] |
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| ln Vitro |
When it comes to 5-HT2 receptors, trimipramine maleate has a far stronger affinity than 5-HT1C receptors [1]. Trimipramine maleate has an IC50 value of 2.11 μM and 4.99 μM, respectively, which indicates that it moderately inhibits human NAT and SERT [2]. It can stand in for trimipramine maleate's antidepressant goal (1 mM-1 μM, 0.1 μM; 10 minutes; HEK293 cells) [2].
1. In vitro receptor binding assays showed that Trimipramine maleate exhibited antiserotonergic properties by interacting with 5-HT1C receptors. [1] 2. In vitro transporter inhibition assays demonstrated that Trimipramine maleate inhibited human SERT, NET, and DAT with Ki values of 14.6 nM, 2.3 nM, and 101 nM, respectively; it also inhibited human OCT1, OCT2, and OCT3 with Ki values of 1.1 μM, 0.4 μM, and 0.9 μM, respectively. Its inhibition on these transporters was weaker than that of its main metabolites for some targets. [2] 3. In vitro binding assays revealed that Trimipramine maleate bound to dopamine D2 receptors, 5-HT2 receptors, and tryptamine binding sites in rat brain tissue homogenates. [3] |
| ln Vivo |
Trimipraminemaleate (5 mg/kg/d; 14 d; long-term medication) has the following physiological effects: 1. Elevate the 5-HT concentration in the area. Olfactory 2 and the prefrontal cortex have the highest levels of 5-HT, followed by the hippocampus. decreased density of 5-HT2 grabbers in the striatum DA D2 and frontal brain. 3. The hypothalamus and nodule. As a result, it has been demonstrated that both 5-HT2 and DA D2 receptors have increased rates of dopamine (DA) and 5-HT production [3].
Chronic administration of Trimipramine maleate to rats increased the levels of norepinephrine metabolite MHPG and serotonin metabolite 5-HIAA in some brain regions, decreased the binding capacity (Bmax) of dopamine D2 receptors and tryptamine binding sites in specific brain areas, and had no significant effect on 5-HT2 receptor binding. [3] |
| Enzyme Assay |
1. For 5-HT1C receptor binding assay: Brain tissues were homogenized and centrifuged to prepare crude membrane fractions. The fractions were incubated with radioactive ligand and different concentrations of Trimipramine maleate at a specific temperature for a set duration. After incubation, the mixture was filtered to separate bound and free ligands, and the radioactivity of bound ligand was measured to calculate the binding affinity of Trimipramine maleate for 5-HT1C receptors. [1]
2. For monoamine transporter inhibition assay: Cell membranes expressing human SERT, NET, or DAT were incubated with radioactive neurotransmitters (e.g., [3H]-5-HT for SERT) and various concentrations of Trimipramine maleate. After incubation, unbound neurotransmitters were removed by filtration, and the radioactivity of bound neurotransmitters was detected to determine the inhibition potency (Ki) of Trimipramine maleate. [2] 3. For dopamine D2/5-HT2/tryptamine binding site assay: Rat brain tissues were homogenized to obtain membrane preparations, which were incubated with respective radioactive ligands and Trimipramine maleate at a controlled temperature. After incubation, the mixture was filtered, and the radioactivity of bound ligand was measured to assess the binding interaction. [3] |
| Cell Assay |
For OCT inhibition assay: Cells stably expressing human OCT1, OCT2, or OCT3 were cultured and incubated with radioactive organic cation substrate and different concentrations of Trimipramine maleate for a certain time. After incubation, cells were washed to remove unincorporated substrate, and the radioactivity inside cells was measured to evaluate the inhibition effect of Trimipramine maleate on OCT-mediated substrate uptake. [2]
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| Animal Protocol |
Animal/Disease Models: Male Wistar rats (220-250 g); osmotic minipump [3] implanted subcutaneously (sc) (sc) in the dorsal thoracic interscapular area
Doses: 5 mg/kg/day Route of Administration: delivered by osmotic minipump; 14 days Experimental Results: The number of 5-HT2 receptors in the frontal cortex and DA D2 receptors in the striatum was diminished, thereby blocking the uptake of 5-HT and dopamine (DA). Rats were divided into control and Trimipramine maleate treatment groups. The treatment group received Trimipramine maleate via oral gavage once daily for a chronic period. At the end of treatment, rats were sacrificed, brains were removed and dissected into specific regions, which were used for biogenic amine metabolite detection (HPLC) and receptor binding assay. [3] |
| References |
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| Additional Infomation |
Trimipramine maleate is the maleate salt form of trimipramine, a dibenzodiazepine tricyclic secondary amine with antidepressant effects. Trimipramine maleate appears to inhibit the transport of serotonin and the uptake of norepinephrine at nerve endings. This increases the availability of norepinephrine or serotonin and prolongs its duration of action. It is a tricyclic antidepressant similar to imipramine but with stronger antihistamine and sedative effects. See also: Trimipramine (containing the active moiety). 1. Trimipramine maleate is an antidepressant whose antiserotonergic effects through 5-HT1C receptors may contribute to its treatment of depression. [1] 2. Trimipramine maleate has lower inhibitory potency against human transport proteins than its main active metabolite, suggesting that the metabolite may contribute to its pharmacological effects in vivo. [2]
3. Long-term use of trimipramine maleate can induce adaptive changes in the central nervous system of rats, which may be related to its slow onset of action in the treatment of depression. [3] |
| Molecular Formula |
C20H26N2.C4H4O4
|
|---|---|
| Molecular Weight |
410.506
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| Exact Mass |
410.22
|
| CAS # |
521-78-8
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| Related CAS # |
Trimipramine;739-71-9;Trimipramine-d3 maleate;1185245-93-5
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| PubChem CID |
5282318
|
| Appearance |
White to off-white solid powder
|
| Density |
1.029g/cm3
|
| Boiling Point |
411.8ºC at 760mmHg
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| Melting Point |
141-143ºC
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| Flash Point |
183.3ºC
|
| LogP |
3.897
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
30
|
| Complexity |
436
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(CN1C2=CC=CC=C2CCC3=CC=CC=C31)CN(C)C.C(=C\C(=O)O)\C(=O)O
|
| InChi Key |
YDGHCKHAXOUQOS-BTJKTKAUSA-N
|
| InChi Code |
InChI=1S/C20H26N2.C4H4O4/c1-16(14-21(2)3)15-22-19-10-6-4-8-17(19)12-13-18-9-5-7-11-20(18)22;5-3(6)1-2-4(7)8/h4-11,16H,12-15H2,1-3H3;1-2H,(H,5,6)(H,7,8)/b;2-1-
|
| Chemical Name |
(Z)-but-2-enedioic acid;3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N,N,2-trimethylpropan-1-amine
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~243.60 mM)
H2O : ~14.29 mg/mL (~34.81 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.09 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 (6.09 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 (6.09 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: 5.88 mg/mL (14.32 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4360 mL | 12.1800 mL | 24.3599 mL | |
| 5 mM | 0.4872 mL | 2.4360 mL | 4.8720 mL | |
| 10 mM | 0.2436 mL | 1.2180 mL | 2.4360 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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