Compared to 5-HT1C receptors, trimipramine has a substantially higher affinity for 5-HT2 receptors [1]. Trimipramine has an IC50 value of 2.11 μM for human SERT and 4.99 μM for human NAT, making it a moderate inhibitor of these enzymes [2]. The antidepressant effects of trimipramine (1 mM, 0.1 mM, 0.01 mM, 1 μM, 0.1 μM; 10 min; HEK293 cells) may have an effect on SERT and NAT [2].

The following are the long-term effects of trimipramine (5 mg/kg/d; 14 days) in rats: 1. Concentration of 5-HT rises regionally. The hippocampus and frontal cortex had the highest levels of 5-HT, followed by the hypothalamus and olfactory tubercle. 2. Decrease the quantity of DA D2 receptors in the striatum and 5-HT2 receptors in the frontal brain. 3. elevated metabolite and monoamine levels in specific brain areas. Therefore, it is hypothesized that there is a higher rate of dopamine (DA) and 5-HT production, which is compatible with adaptive down-regulation of D2 and 5-HT2 receptors [3].

Animal/Disease Models: Male Wistar rat (220-250 g); osmotic minipump is implanted subcutaneously (sc) (sc) in the dorsal thoracic interscapular area [3]
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).

Absorption, Distribution and Excretion
Rapid Absorption

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Metabolism/Metabolites
Liver
Liver
Half-life: 11-18 hours

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Biological Half-life
11-18 hours

Toxicity Summary
Trimipramine's mechanism of action differs from other tricyclic antidepressants. Trimipramine works by reducing the reuptake of norepinephrine and serotonin (5-HT). Hepatotoxicity
Liver dysfunction is uncommon in patients taking trimipramine in clinical trials (Probability score: D (likely a rare cause of clinically significant liver injury)). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Since there is no published experience with the use of trimipramine during lactation, alternative medications may be preferred, especially for breastfed newborns or premature infants. ◉ Effects on Breastfed Infants As of the revision date, no published information on trimipramine was found. A study of 20 breastfed infants born to mothers taking tricyclic antidepressants, followed for 1 to 3 years, found no adverse effects on the infants' growth and development. Two small controlled studies suggest that the effects of other tricyclic antidepressants on breastfed infants may be related to the use of tramipram. Antidepressants have no adverse effects on infant development. Another study formally tested 25 infants of mothers who took tricyclic antidepressants during pregnancy and lactation for 15 to 71 months, finding that these infants grew and developed normally. However, none of the mothers in all these studies took tramipram.
◉ Effects on Lactation and Breast Milk
Tramipramine increases serum prolactin levels and causes at least one case of galactorrhea. For mothers who have established lactation, their prolactin levels may not affect their ability to breastfeed.
An observational study investigated the outcomes of 2,859 women who took antidepressants in the two years prior to pregnancy. Compared to women who did not take antidepressants during pregnancy, mothers who took antidepressants in all three stages of pregnancy were 37% less likely to breastfeed at discharge. Mothers who took antidepressants only in the third trimester were 75% less likely to breastfeed at discharge. The likelihood of breastfeeding at discharge was lower. Mothers who took antidepressants only in the first and second trimesters were not less likely to breastfeed at discharge. The study did not specify the type of antidepressant used by the mothers. A retrospective cohort study analyzed hospital electronic medical records from 2001 to 2008, comparing women who took antidepressants in late pregnancy (n = 575), women with mental illness but not taking antidepressants (n = 1552), and mothers without a diagnosed mental illness (n = 30,535). Women taking antidepressants were 37% less likely to breastfeed at discharge than women without a diagnosed mental illness, but there was no difference in the likelihood of breastfeeding compared to mothers with untreated mental illness. None of the mothers were taking trimethoprim. A study of 80,882 Norwegian women in a mother-infant paired study from 1999 to 2008 included 392 women who reported new postpartum use of antidepressants and 201 women who reported starting antidepressants during pregnancy. Compared to the control group unexposed to antidepressants, antidepressant use in late pregnancy was associated with a 7% decrease in breastfeeding initiation rate, but had no effect on the duration of breastfeeding or exclusive breastfeeding rate. Compared to the control group unexposed to antidepressants, new use or restart of antidepressant use was associated with a 63% decrease in primary breastfeeding rate and a 51% decrease in any breastfeeding rate at 6 months, along with a 2.6-fold increased risk of abrupt cessation of breastfeeding. Specific antidepressants used were not mentioned.

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Protein binding
93%-96% (bound to plasma proteins)

[1]. Evidence for a role of 5-HT1C receptors in the antiserotonergic properties of some antidepressant drugs. Eur J Pharmacol. 1993 Feb 9. 231(2):223-9.

[2]. Inhibitory potencies of trimipramine and its main metabolites at human monoamine and organic cation transporters. Psychopharmacology (Berl). 2011 Sep. 217(2):289-95.

[3]. The effects of chronic trimipramine treatment on biogenic amine metabolism and on dopamine D2, 5-HT2 and tryptamine binding sites in rat brain. Gen Pharmacol. 1990. 21(5):759-62.

Trimipramine is a dibenzodiazepine compound with the chemical name 10,11-dihydro-5H-dibenzo[b,f]azazepine, where the nitrogen atom is substituted with a 3-(dimethylamino)-2-methylpropyl group. It is used as an antidepressant. It is both an antidepressant and an environmental pollutant and exogenous substance. It is a dibenzodiazepine compound and also a tertiary amine compound. Functionally, it is related to imipramine. Trimipramine is a tricyclic antidepressant, similar to imipramine but with stronger antihistamine and sedative effects. Trimipramine is a tricyclic antidepressant. Trimipramine is a tricyclic antidepressant used to treat major (endogenous) depression and reactive (exogenous) depression. In clinical trials, trimipramine treatment was not associated with an increased rate of serum transaminase elevation, nor was it found to be associated with clinically significant cases of acute liver injury. Trimipramine is only present in individuals who have used or taken this drug. It is a tricyclic antidepressant, similar to imipramine, but with stronger antihistamine and sedative effects. [PubChem] Trimipramine's mechanism of action differs from other tricyclic antidepressants. Trimipramine works by reducing the reuptake of norepinephrine and serotonin (5-HT).
A tricyclic antidepressant similar to imipramine, but with stronger antihistamine and sedative effects.
See also: Trimipramine maleate (in salt form); Trimipramine mesylate (its active ingredient).
Indications
For the treatment of depression and depression accompanied by anxiety, agitation, or sleep disturbances.
FDA Label
Mechanism of Action
Trimipramine's mechanism of action differs from other tricyclic antidepressants. Trimipramine works by reducing the reuptake of norepinephrine and serotonin (5-HT).

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Pharmacodynamics
Tribipram is a tricyclic antidepressant. The mechanism of action of tricyclic antidepressants was once thought to be the inhibition of the reuptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, while this effect occurred immediately, mood improvement took approximately two weeks. It is now believed that altered receptor sensitivity occurs in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, the part of the brain associated with mood. Presynaptic receptors are affected: α1 and β1 receptors are sensitized, and α2 receptors are desensitized (leading to increased norepinephrine production). Tricyclic antidepressants are also known effective analgesics used to treat various types of pain, especially neuropathic pain or neuralgia. The exact mechanism of their analgesic effect is unclear, but they are generally believed to regulate the anti-opioid system in the central nervous system through an indirect serotonergic pathway. They are also effective in preventing migraines, but do not terminate acute migraine attacks. Their anti-migraine mechanism is also thought to be serotonergic.

C20H26N2

294.442

294.21

739-71-9

Trimipramine maleate;521-78-8;Trimipramine-d3 (N-methyl-d3)

5584

Typically exists as solid at room temperature

0.9912 (rough estimate)

426.2°C (rough estimate)

45°

9℃

1.6450 (estimate)

4.186

0

2

4

22

317

0

CC(CN(C)C)CN1C2=CC=CC=C2CCC3=CC=CC=C31

ZSCDBOWYZJWBIY-UHFFFAOYSA-N

InChI=1S/C20H26N2/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/h4-11,16H,12-15H2,1-3H3

3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N,N,2-trimethylpropan-1-amine

Surmontil, Rhotrimine, Stangyl; Trimipramine

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.

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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).

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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)

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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).

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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

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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.

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