Absorption, Distribution and Excretion
They are well absorbed in the digestive tract.
Phenothiazines have an extremely long final residence time in the body. Multiple metabolites can still be detected in urine six months after discontinuation of these drugs. /Phenothiazines/
Metabolism/Metabolites

Hepatic
In rats, 10-(3-dimethylamino-2-methylpropyl)phenothiazine sulfoxide and 10-(3-methylamino-2-methylpropyl)phenothiazine are produced; HEWICK, DS, & BECKETT, AH, BIOCHEM J, 122, 56P (1971). /Excerpt from Table/
Primarily metabolized in the liver. Hepatic metabolic reactions include oxidation, hydroxylation, demethylation, sulfoxide formation, and conjugation with glucuronic acid. Side chains may also undergo metabolic alterations. /Human, Oral/. /Tartrate/

Interactions
...significantly enhances the respiratory depression induced by meperidine. The enhanced effects of many drugs (especially central nervous system depressants) are not due to inhibition of hepatic microsomal enzymes. In fact, phenothiazines promote the induction of these enzymes. /Phenothiazines/
may increase the toxicity of organophosphates or other acetylcholinesterase inhibitors and procaine. Do not use adrenaline to counteract their hypotensive or depressive effects, as it will enhance these effects.
Severe hypothermia may occur...in patients receiving/concurrently/antipyretic treatment...its effects may be enhanced when used in combination with central nervous system depressants (such as atropine, antihypertensive drugs, anesthetics, barbiturates...other sedatives, anesthetics, tranquilizers...alcohol). /Tartrates/

[1]. Bioanalytical method development and validation of alimemazine in human plasma by LC-MS/MS and its application in bioequivalence studies. J Pharm Bioallied Sci. 2013 Oct;5(4):257-64.

[2]. Trimeprazine increases IRS2 in human islets and promotes pancreatic β cell growth and function in mice. JCI Insight. 2016;1(3).

Trimeprazole belongs to the phenothiazine class of drugs. It is a phenothiazine derivative used as an antipruritic. See also: Trimeprazole tartrate (note moved to). Drug Indications For the prevention and relief of allergic diseases causing pruritus (itching) and urticaria (certain allergic skin reactions). Mechanism of Action Trimeprazole competitively binds to HA receptor sites with free histamine. This antagonizes the effect of histamine on HA receptors, thereby alleviating the negative symptoms caused by histamine binding to HA receptors.

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Therapeutic Uses
Antipruritic Drugs
Its sedative effect is relatively weak…/Tartrates/
It is considered effective in treating itching symptoms caused by urticaria; may be effective in relieving nasal allergy symptoms; may be effective in long-term relief of itching symptoms caused by various allergic and non-allergic diseases…/Tartrates/
…may be effective in long-term relief of itching symptoms…including neurodermatitis, contact dermatitis, pityriasis rosea, poison ivy dermatitis, eczematous dermatitis, anal and vulvar pruritus, drug eruptions and chickenpox…/Tartrates/
For more complete data on the therapeutic uses of trimerazine (8 types), please visit the HSDB record page.

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Drug Warnings
Side effects are often a consequence of many pharmacological actions of drugs…the most important drugs are those that act on the central nervous system, cardiovascular system, autonomic nervous system and endocrine function. …The most dangerous side effects…are caused by allergic reactions, especially blood disorders. /Phenothiazines/
Sedative and mild sedative effects may also occur. Symptoms of overdose include dizziness…and central nervous system depression, eventually leading to coma. Veterinarians: Avoid rapid intravenous and intra-arterial injections in animals. Drowsiness is the most common reaction. All precautions applicable to phenothiazines should be followed. /Tartrates/ For more complete data on drug warnings for trimepazine (9 of 9), please visit the HSDB records page.

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Pharmacodynamics
Trimeprazine (also known as alimerazine) is a tricyclic antihistamine with a structure similar to phenothiazines, but differs in ring substitution and chain characteristics. Trimeprazine belongs to the same class of drugs as chlorpromazine (Thorazine) and stelazine; however, unlike other drugs in this class, trimepazine is not used clinically as an antipsychotic. It has antihistamine, sedative, and antiemetic (antinausea) effects. Trimeprazole is primarily used as an antiemetic, to prevent motion sickness, or in combination with other medications as an antihistamine in cough and cold remedies. Tricyclic antihistamines are structurally related to tricyclic antidepressants, which explains the antihistamine side effects of both classes and the poor tolerability of tricyclic H1 receptor antagonists.

C18H22N2S

298.45

298.15

84-96-8

Alimemazine-d6;1346603-88-0

5574

CRYSTALS

1.203 g/cm3

420.3ºC at 760mmHg

68°C

208ºC

4.552

0

3

4

21

311

0

CC(CN(C)C)CN1C2=CC=CC=C2SC3=CC=CC=C31

ZZHLYYDVIOPZBE-UHFFFAOYSA-N

InChI=1S/C18H22N2S/c1-14(12-19(2)3)13-20-15-8-4-6-10-17(15)21-18-11-7-5-9-16(18)20/h4-11,14H,12-13H2,1-3H3

N,N,2-trimethyl-3-phenothiazin-10-ylpropan-1-amine

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.)