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
Hepatic
Hepatic
Half Life: 11-18 hrs

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Biological Half-Life
11-18 hrs

Toxicity Summary
Trimipramine's mechanism of action differs from other tricyclic antidepressants. Trimipramine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).

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Hepatotoxicity
In clinical trials, liver test abnormalities were uncommon in patients taking trimipramine (
Likelihood score: D (possible rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because there is no published experience with trimipramine during breastfeeding, other agents may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Published information on trimipramine was not found as of the revision date. Follow-up for 1 to 3 years in a group of 20 breastfed infants whose mothers were taking a tricyclic antidepressant found no adverse effects on growth and development. Two small controlled studies indicate that other tricyclic antidepressants have no adverse effect on infant development. In another study, 25 infants whose mothers took a tricyclic antidepressant during pregnancy and lactation were tested formally between 15 to 71 months and found to have normal growth and development. However, none of the mothers in any of these studies took trimipramine.
◉ Effects on Lactation and Breastmilk
Trimipramine increases serum prolactin levels and has caused at least one case of galactorrhea. The maternal prolactin level in a mother with established lactation may not affect her ability to breastfeed.
An observational study looked at outcomes of 2859 women who took an antidepressant during the 2 years prior to pregnancy. Compared to women who did not take an antidepressant during pregnancy, mothers who took an antidepressant during all 3 trimesters of pregnancy were 37% less likely to be breastfeeding upon hospital discharge. Mothers who took an antidepressant only during the third trimester were 75% less likely to be breastfeeding at discharge. Those who took an antidepressant only during the first and second trimesters did not have a reduced likelihood of breastfeeding at discharge. The antidepressants used by the mothers were not specified.
A retrospective cohort study of hospital electronic medical records from 2001 to 2008 compared women who had been dispensed an antidepressant during late gestation (n = 575) to those who had a psychiatric illness but did not receive an antidepressant (n = 1552) and mothers who did not have a psychiatric diagnosis (n = 30,535). Women who received an antidepressant were 37% less likely to be breastfeeding at discharge than women without a psychiatric diagnosis, but no less likely to be breastfeeding than untreated mothers with a psychiatric diagnosis. None of the mothers were taking trimipramine.
In a study of 80,882 Norwegian mother-infant pairs from 1999 to 2008, new postpartum antidepressant use was reported by 392 women and 201 reported that they continued antidepressants from pregnancy. Compared with the unexposed comparison group, late pregnancy antidepressant use was associated with a 7% reduced likelihood of breastfeeding initiation, but with no effect on breastfeeding duration or exclusivity. Compared with the unexposed comparison group, new or restarted antidepressant use was associated with a 63% reduced likelihood of predominant, and a 51% reduced likelihood of any breastfeeding at 6 months, as well as a 2.6-fold increased risk of abrupt breastfeeding discontinuation. Specific antidepressants were not mentioned.

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Protein Binding
93%-96% (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 dibenzoazepine that is 10,11-dihydro-5H-dibenzo[b,f]azepine substituted by a 3-(dimethylamino)-2-methylpropyl group at the nitrogen atom. It is used as an antidepressant. It has a role as an antidepressant, an environmental contaminant and a xenobiotic. It is a dibenzoazepine and a tertiary amino compound. It is functionally related to an imipramine.
Tricyclic antidepressant similar to imipramine, but with more antihistaminic and sedative properties.
Trimipramine is a Tricyclic Antidepressant.
Trimipramine is a tricyclic antidepressant used in the therapy of major (endogenous) as well as reactive (exogenous) depression. In clinical trials, trimipramine therapy was not associated with an increased rate of elevations in serum aminotransferase levels, and it has yet to be linked to instances of clinically apparent acute liver injury.
Trimipramine is only found in individuals that have used or taken this drug. It is a tricyclic antidepressant similar to imipramine, but with more antihistaminic and sedative properties. [PubChem]Trimipramine's mechanism of action differs from other tricyclic antidepressants. Trimipramine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).
Tricyclic antidepressant similar to IMIPRAMINE, but with more antihistaminic and sedative properties.
See also: Trimipramine Maleate (has salt form); Trimipramine Mesylate (is active moiety of).

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Drug Indication
For the treatment of depression and depression accompanied by anxiety, agitation or sleep disturbance
FDA Label

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Mechanism of Action
Trimipramine's mechanism of action differs from other tricyclic antidepressants. Trimipramine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).

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Pharmacodynamics
Trimipramine is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: a1 and b1 receptors are sensitized, a2 receptors are desensitised (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. A precise mechanism for their analgesic action is unknown, but it is thought that they modulate anti-pain opioid systems in the CNS via an indirect serotonergic route. They are also effective in migraine prophylaxis, but not in abortion of acute migraine attack. The mechanism of their anti-migraine action 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.)