 Chemical Structure.png)
Trifluoperazine dihydrochloride (TFP; SKF5019), a typical phenothiazine class of antipsychotic mainly used to treat schizophrenia, is a dopamine D2 receptor inhibitor with IC50 of 1.1 NM. Trifluoperazine binds to α1A- and α1B-adrenoceptor with Ki value of 27.6 nM and 19.2 nM, respectively, with α1B/α1A ratio of 0.7. Trifluoperazine inhibits Mycobacterium tuberculosis (Mtb) with MICs of 7.6 μg/mL. Trifluoperazine (< 14.78 mM) suppresses the activities of the mouse splenic NK cell cytotoxicity and the effector-target cell conjugation in a dose dependent manner.
Physicochemical Properties
| Molecular Formula | C21H24F3N3S.2HCL | |
| Molecular Weight | 480.42 | |
| Exact Mass | 479.117 | |
| CAS # | 440-17-5 | |
| Related CAS # | Trifluoperazine;117-89-5;Trifluoperazine dimaleate;605-75-4 | |
| PubChem CID | 5566 | |
| Appearance | White to off-white solid powder | |
| Boiling Point | 506ºC at 760 mmHg | |
| Melting Point | 243 °C (dec.)(lit.) | |
| Flash Point | 259.8ºC | |
| Vapour Pressure | 2.32E-10mmHg at 25°C | |
| LogP | 6.49 | |
| Hydrogen Bond Donor Count | 0 | |
| Hydrogen Bond Acceptor Count | 7 | |
| Rotatable Bond Count | 4 | |
| Heavy Atom Count | 28 | |
| Complexity | 510 | |
| Defined Atom Stereocenter Count | 0 | |
| InChi Key | ZEWQUBUPAILYHI-UHFFFAOYSA-N | |
| InChi Code | 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 | |
| Chemical Name | 10-[3-(4-methylpiperazin-1-yl)propyl]-2-(trifluoromethyl)phenothiazine | |
| Synonyms |
|
|
| HS Tariff Code | 2934.99.9001 | |
| 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) |
Biological Activity
| ln Vitro | Long-standing and commonly used, trifluoperazine dihydrochloride is a "conventional" antipsychotic medication. Trifluoperazine dihydrochloride is a calmodulin inhibitor that has been the subject of much research[3][4]. Trifluoperazine dihydrochloride disrupts cellular CaM and/or CaM-dependent processes to operate as a reversible inhibitor of influenza virus morphogenesis, but not budding[5]. | ||
| ln Vivo |
|
||
| Animal Protocol |
|
||
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion ULTIMATE SOJOURN OF PHENOTHIAZINE DRUGS IN BODY IS EXCEEDINGLY LONG. /PHENOTHIAZINES/ 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 Biological Half-Life 10-20 hours |
||
| Toxicity/Toxicokinetics |
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. 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). 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. 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. Non-Human Toxicity Values LD50 Mouse ip 175 mg/kg |
||
| References |
[1]. 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. [2]. 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. [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. |
||
| Additional Infomation |
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). Drug Indication For the treatment of anxiety disorders, depressive symptoms secondary to anxiety and agitation. 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/ 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. 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. 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. |
Solubility Data
| Solubility (In Vitro) |
|
|||
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.20 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 (5.20 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.20 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0815 mL | 10.4076 mL | 20.8151 mL | |
| 5 mM | 0.4163 mL | 2.0815 mL | 4.1630 mL | |
| 10 mM | 0.2082 mL | 1.0408 mL | 2.0815 mL |