Trifluoperazine is a widely used, "traditional" antipsychotic medication with a lengthy history. One extensively researched medication that has been utilized as a calmodulin inhibitor is trifluoperazine [3][4]. Trifluoperazine interferes with cellular CaM and/or CaM-dependent processes to operate as a reversible inhibitor of influenza virus morphogenesis, but not budding [5].

Absorption, Distribution and Excretion
ULTIMATE SOJOURN OF PHENOTHIAZINE DRUGS IN BODY IS EXCEEDINGLY LONG. /PHENOTHIAZINES/

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Metabolism / Metabolites
Hepatic.
AFTER CHRONIC ADMIN OF PIPERAZINE-SUBSTITUTED PHENOTHIAZINE DRUGS...TO RATS, TISSUES CONTAINED DRUG METABOLITES, IN WHICH PIPERAZINE RING FISSION BY MULTIPLE OXIDATIVE N-DEALKYLATION HAD OCCURRED TO GIVE SUBSTITUTED ETHYLENEDIAMINE. ...2-TRIFLUOROMETHYL ANALOGUE WAS FORMED SIMILARLY FROM TRIFLUPERAZINE.
IN VIVO DEGRADATION OF PIPERAZINE RING OF TRIFLUOPERAZINE LEADS TO FORMATION OF GAMMA-(PHENOTHIAZINYL-10)-PROPYLAMINE & ITS RING SUBSTITUTED ANALOGS CF3- & CL-. SULFOXIDES OF THESE METABOLITES HAVE BEEN IDENTIFIED AS URINARY BIOTRANSFORMATION PRODUCTS IN RATS (CHRONIC).
Hepatic.
Half Life: 10-20 hours

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Biological Half-Life
10-20 hours

Toxicity Summary
Trifluoperazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.

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Hepatotoxicity
Liver test abnormalities have been reported to occur in a high proportion of patients on long term phenothiazine therapy, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually mild, asymptomatic and transient, reversing even with continuation of medication. Rare instances of clinically apparent acute liver injury, resembling that due to chlorpromazine, have been reported with trifluoperazine therapy. The onset of jaundice is usually within 1 to 4 weeks, and the pattern of serum enzyme elevations is typically cholestatic or mixed. Immunoallergic features (rash, fever and eosinophilia) were present in some cases but were mild and self-limited; autoantibodies were rare.
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
Limited information indicates that maternal doses of trifluoperazine up to 10 mg daily do not affect the breastfed infant. Very limited long-term follow-up data indicate no adverse developmental effects when other phenothiazines are used alone. A safety scoring system finds trifluoperazine to be not recommended during breastfeeding. Because there is little published experience with trifluoperazine during breastfeeding, other antipsychotic agents may be preferred, especially wile nursing an newborn or preterm infant.
◉ Effects in Breastfed Infants
Two mothers taking trifluoperazine 5 and 10 mg per day orally breastfed their infants from 1 week and 8 weeks of age, respectively. Mental and psychomotor development were measured at various time up to 30 months of age and were found to be normal.
One infant was breastfed from birth during maternal trifluoperazine 10 mg daily in addition to clonazepam 0.25 mg daily and valproic acid 500 mg daily. No adverse effects in the infant were reported by the mother (follow-up time unspecified).
One mother began taking trifluoperazine (dosage unspecified) 2 months postpartum while breastfeeding her infant. She also started olanzapine 10 mg daily, paroxetine and procyclidine (dosages unspecified). The infant experiences no adverse reactions.
◉ Effects on Lactation and Breastmilk
Phenothiazines cause galactorrhea in 26 to 40% of female patients. Hyperprolactinemia appears to be the cause of the galactorrhea. The hyperprolactinemia is caused by the drug's dopamine-blocking action in the tuberoinfundibular pathway.

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Interactions
Additive QT interval prolongation may increase the risk of ventricular tachycardia when /probucol is used with phenothiazines/. /Phenothiazines/
Concurrent use /of other photosensitizing medications/ with phenothiazines may cause additive photosensitizing effects. In addition, concurrent use of systemic methoxsalen, trixsalen, or tetracyclines with phenothiazines may potentiate intraocular photochemical damage to the choroid, retina, or lens. /Phenothiazines/
Prior administration of phenothiazines may decrease the pressor effect and shorten the duration of action of phenylephrine. /Phenothiazines/
In addition to increased CNS and respiratory depression, concurrent use /of opiod (narcotic) analgesics/ with phenothiazines increases orthostatic hypotension and increases the risk of severe constipation, which may lead to paralytic ileus, and/or urinary retention. /Phenothiazines/
For more Interactions (Complete) data for TRIFLUOPERAZINE (29 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Mouse ip 175 mg/kg

[1]. Huerta-Bahena J, Villalobos-Molina R, García-Sáinz JA. Trifluoperazine and chlorpromazine antagonize alpha 1- but not alpha2- adrenergic effects. Mol Pharmacol. 1983;23(1):67-70.

[2]. Ligand-based design identifies a potent NUPR1 inhibitor exerting anticancer activity via necroptosis. J Clin Invest. 2019;129(6):2500-2513. Published 2019 Mar 28.

[3]. Marques LO, Lima MS, Soares BG. Trifluoperazine for schizophrenia. Cochrane Database Syst Rev. 2004;2004(1):CD003545.

[4]. Howland RH. Trifluoperazine: A Sprightly Old Drug. J Psychosoc Nurs Ment Health Serv. 2016;54(1):20-22.

[5]. Influence of trifluoperazine on the late stage of influenza virus infection in MDCK cells. Antiviral Res. 1991;15(2):149-160.

Trifluoperazine is a member of the class of phenothiazines that is phenothiazine having a trifluoromethyl subsitituent at the 2-position and a 3-(4-methylpiperazin-1-yl)propyl group at the N-10 position. It has a role as a dopaminergic antagonist, an antiemetic, an EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor, an EC 5.3.3.5 (cholestenol Delta-isomerase) inhibitor, a calmodulin antagonist and a phenothiazine antipsychotic drug. It is a N-alkylpiperazine, a N-methylpiperazine, a member of phenothiazines and an organofluorine compound.
A phenothiazine with actions similar to chlorpromazine. It is used as an antipsychotic and an antiemetic.
Trifluoperazine is a Phenothiazine.
Trifluoperazine is a phenothiazine and antipsychotic agent that no longer commonly used in clinical practice. Trifluoperazine is a rare cause of clinically apparent acute cholestatic liver injury.
Trifluoperazine has been reported in Crotalaria pallida with data available.
Trifluoperazine is a phenothiazine derivative and a dopamine antagonist with antipsychotic and antiemetic activities. Trifluoperazine exerts its antipsychotic effect by blocking central dopamine receptors, thereby preventing effects such as delusions and hallucinations caused by an excess of dopamine. This agent also functions as a calmodulin inhibitor, thereby leading to elevation of cytosolic calcium.
Trifluoperazine is only found in individuals that have used or taken this drug. It is a phenothiazine with actions similar to chlorpromazine. It is used as an antipsychotic and an antiemetic. [PubChem]Trifluoperazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.
A phenothiazine with actions similar to CHLORPROMAZINE. It is used as an antipsychotic and an antiemetic.
See also: Phenothiazine (subclass of); Trifluoperazine Hydrochloride (has salt form); Trifluoperazine dimaleate (is active moiety of).

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Drug Indication
For the treatment of anxiety disorders, depressive symptoms secondary to anxiety and agitation.

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Mechanism of Action
Trifluoperazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.
...PHENOTHIAZINES, BLOCK DOPAMINE RECEPTORS & INCR TURNOVER RATE OF DOPAMINE IN CORPUS STRIATUM. INCR TURNOVER RATE IS BELIEVED TO BE RESULT OF NEURONAL FEEDBACK MECHANISM. ...OF IDENTIFIED DOPAMINERGIC NEURONS IN SUBSTANTIA NIGRA & VENTRAL TEGMENTAL AREAS. SPONTANEOUS FIRING OF THESE CELLS IS INCR... /PHENOTHIAZINES/

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Therapeutic Uses
Antiemetics; Antipsychotic Agents, Phenothiazine; Dopamine Antagonists
IN THE TREATMENT OF ACUTE PSYCHOSES, THE DOSE OF ANTIPSYCHOTIC DRUG IS INCREASED DURING THE FIRST FEW DAYS TO ACHIEVE CONTROL OF SYMPTOMS. THE DOSE IS THEN ADJUSTED DURING THE NEXT SEVERAL WEEKS AS THE PATIENT'S CONDITION WARRANTS. /PHENOTHIAZINES/
The use of antipsychotic drugs in mania and depression has met with some success. /PHENOTHIAZINES/
...TRIFLUOPERAZINE...REPORTED EFFECTIVE IN SEVERELY IMPAIRED AUTISTIC CHILDREN, & DIFFERENTIAL DIAGNOSIS OF THIS GROUP FROM SO-CALLED MINIMAL-BRAIN-DAMAGE (MBD) SYNDROME IN CHILDREN IS ESSENTIAL.
For more Therapeutic Uses (Complete) data for TRIFLUOPERAZINE (10 total), please visit the HSDB record page.

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Drug Warnings
PHENOTHIAZINES SHOULD BE USED WITH EXTREME CAUTION, IF @ ALL, IN UNTREATED EPILEPTIC PT & IN PT UNDERGOING WITHDRAWAL FROM CENTRAL DEPRESSANT DRUGS SUCH AS ALCOHOL & BARBITURATES. /PHENOTHIAZINES/
...FEW PT WITH ANGINA PECTORIS HAVE REPORTED INCR PAIN DURING THERAPY WITH TRIFLUOPERAZINE. THEREFORE, PT WITH ANGINA SHOULD BE OBSERVED CAREFULLY & DRUG WITHDRAWN IF UNFAVORABLE RESPONSE OCCURS. /HYDROCHLORIDE/
SAFE USE...DURING PREGNANCY HAS NOT BEEN ESTABLISHED WITH RESPECT TO POSSIBLE ADVERSE EFFECTS ON FETAL DEVELOPMENT. ...PHENOTHIAZINES... SHOULD BE USED WITH EXTREME CAUTION IN PT WITH HISTORY OF GLAUCOMA OR PROSTATIC HYPERTROPHY. /PHENOTHIAZINES/
ROUTINE ADMIN OF ANTIPARKINSONISM AGENTS SHOULD BE AVOIDED WITH MOST ANTIPSYCHOTIC DRUG REGIMENS. /PHENOTHIAZINES/
For more Drug Warnings (Complete) data for TRIFLUOPERAZINE (28 total), please visit the HSDB record page.

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Pharmacodynamics
Trifluoperazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Trifluoperazine has not been shown effective in the management of behaviorial complications in patients with mental retardation.

C21H24N3F3S

407.49556

407.164

117-89-5

Trifluoperazine dihydrochloride;440-17-5;Trifluoperazine dimaleate;605-75-4;Trifluoperazine-d8

5566

Typically exists as solid at room temperature

1.239g/cm3

506ºC at 760mmHg

232°C

2.32E-10mmHg at 25°C

4.886

0

7

4

28

510

0

CN1CCN(CCCN2C3=CC=CC=C3SC4=C2C=C(C=C4)C(F)(F)F)CC1

ZEWQUBUPAILYHI-UHFFFAOYSA-N

InChI=1S/C21H24F3N3S/c1-25-11-13-26(14-12-25)9-4-10-27-17-5-2-3-6-19(17)28-20-8-7-16(15-18(20)27)21(22,23)24/h2-3,5-8,15H,4,9-14H2,1H3

10-[3-(4-methylpiperazin-1-yl)propyl]-2-(trifluoromethyl)phenothiazine

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.)