Perphenazine diHCl (Trilafon; Etaperazine; Perphenazin; Perfenazine; Chlorpiprazine) is an orally bioactive antagonist of dopamine receptor and histamine-1 receptor antagonist with the potential to be used for mental disease, cancer, inflammation. It inhibits dopamine receptor and histamine-1 receptor with Ki values of 0.56 nM (D2), 0.43 nM (D3), .6 nM (5-HT2A), respectively.
Physicochemical Properties
| Molecular Formula | C21H26N3OSCL.2[HCL] |
| Molecular Weight | 476.89052 |
| Exact Mass | 475.102 |
| CAS # | 2015-28-3 |
| Related CAS # | Perphenazine;58-39-9;Perphenazine-d8 dihydrochloride;2070015-23-3 |
| PubChem CID | 74835 |
| Appearance | Typically exists as solid at room temperature |
| Boiling Point | 580.4ºC at 760mmHg |
| Flash Point | 304.8ºC |
| Vapour Pressure | 2.6E-14mmHg at 25°C |
| LogP | 5.487 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 29 |
| Complexity | 463 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C1=CC=C2C(=C1)N(CCCN3CCN(CC3)CCO)C4=C(C=CC(=C4)Cl)S2.Cl.Cl |
| InChi Key | JGTYANSBOIVAMH-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C21H26ClN3OS.2ClH/c22-17-6-7-21-19(16-17)25(18-4-1-2-5-20(18)27-21)9-3-8-23-10-12-24(13-11-23)14-15-26;;/h1-2,4-7,16,26H,3,8-15H2;2*1H |
| Chemical Name | 2-[4-[3-(2-chlorophenothiazin-10-yl)propyl]piperazin-1-yl]ethanol;dihydrochloride |
| 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 |
| 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 | In L02 cells, 40 μM perphenazine dihydrochloride promotes apoptosis mediated by CTSD (Cathepsin D) and reduces cell viability[2]. When perphenazine (30 μM, 24 h) dihydrochloride is added to L02 cells, it causes lysosomal cell death by causing severe vacuolation of the lysosome, defective lysosomal membrane, and lysosomal membrane permeabilization (LMP)[2]. In L02 cells, autophagic flow is inhibited by perphenazine (10–40 μM, 24 h) dihydrochloride[2]. Perphenazine (1 µM, 24 h) dihydrochloride inhibits the migration and invasion of glioblastoma U-87 MG cells[4]. |
| ln Vivo | In ICR mice, perphenazine (oral gavage, 180 mg/kg, every other day for 21 days) dihydrochloride causes damage to the liver and lysosomal membranes[2]. In mouse models of Th2-type allergic dermatitis, perphenazine (oral administration, 10 mg/kg, every other day for 6 days) dihydrochloride attenuates morphological phenotype[3]. |
| Cell Assay |
Cell Viability Assay[2] Cell Types: L02 cells Tested Concentrations: 10-100 μM Incubation Duration: 12, 24, 48 h Experimental Results: Inhibited cell viability in a concentration and time -dependent manner. Western Blot Analysis[2] Cell Types: L02 cells Tested Concentrations: 10, 20, 30, and 40 μM Incubation Duration: 24 h Experimental Results: Increased LC3 I/II and P62/SQSTM1 levels Cell Migration Assay [4] Cell Types: U-87 MG cells Tested Concentrations: 0, 3, 6, 9, 12, and 24 h Incubation Duration: 0, 3, 6, 9, 12, and 24 h Experimental Results: Increased the wound closure in human glioblastoma cell cultures from 24.6 to 62.7%. |
| Animal Protocol |
Animal/Disease Models: ICR mice[2] Doses: 10, 30, 60, 120, 180 mg/kg Route of Administration: po (oral gavage), every other day for 21 days. Experimental Results: Increased histological injury and aminotransferases compared with control. Animal/Disease Models: Oxazolone-treated animal model of dermatitis[3] Doses: 10 mg/kg Route of Administration: Oral administration, every other day for 6 days Experimental Results: diminished The levels of mice ear swelling . |
| References |
[1]. Dopamine and serotonin receptor binding and antipsychotic efficacy. Neuropsychopharmacology. 2007 Aug;32(8):1715-26. [2]. Lysosomal membrane permeabilization mediated apoptosis involve in perphenazine-induced hepatotoxicity in vitro and in vivo. Toxicol Lett. 2022 Jul 29;367:76-87. [3]. Perphenazine Attenuates the Pro-Inflammatory Responses in Mouse Models of Th2-Type Allergic Dermatitis. Int J Mol Sci. 2020 May 3;21(9):3241. [4]. Perphenazine and prochlorperazine decrease glioblastoma U-87 MG cell migration and invasion: Analysis of the ABCB1 and ABCG2 transporters, E-cadherin, α-tubulin and integrins (α3, α5, and β1) levels. Oncol Lett. 2022 Jun;23(6):182. [5]. n vitro anticancer activity of fluphenazine, perphenazine and prochlorperazine. A review. J Appl Toxicol. 2021 Jan;41(1):82-94. |
Solubility Data
| Solubility (In Vitro) | 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 |
| Solubility (In Vivo) |
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. Injection Formulations (e.g. IP/IV/IM/SC) 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). 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) Oral Formulations 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). 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0969 mL | 10.4846 mL | 20.9692 mL | |
| 5 mM | 0.4194 mL | 2.0969 mL | 4.1938 mL | |
| 10 mM | 0.2097 mL | 1.0485 mL | 2.0969 mL |