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| | PERPHENAZINE Basic information |
| | PERPHENAZINE Chemical Properties |
| Melting point | 95-98?C | | Boiling point | bp0.15 214-218°; bp1 278-281° | | density | 1.253 | | refractive index | 1.6100 (estimate) | | storage temp. | 2-8°C | | solubility | Practically insoluble in water, freely soluble in methylene chloride, soluble in ethanol (96 per cent). It dissolves in dilute solutions of hydrochloric acid. | | pka | pKa 7.8(H2O,t =24±1) (Uncertain) | | form | neat | | color | White | | Water Solubility | 28.28mg/L(24 ºC) | | Merck | 14,7183 | | Stability: | Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months. | | CAS DataBase Reference | 58-39-9(CAS DataBase Reference) |
| | PERPHENAZINE Usage And Synthesis |
| Description | Perphenazine (58-39-9) is a clinically useful typical antipsychotic drug. The therapeutic mode of action is not well understood but it binds to a wide variety of receptors including serotonin, histamine, dopamine, and α-adrenergic.1 Perphenazine is an inhibitor of acid sphingomyelinase(ASM)2 and positively affected xenografted tumor growth via perturbation of intracellular cholesterol transport through ASM3. It has also been shown to be an inhibitor of glutamate dehydrogenase.4 | | Chemical Properties | Off-White to Pale Yellow Solid | | Originator | Trilafon, Schering ,US ,1957 | | Uses | immune suppressant, antifungal | | Uses | D2 dopamine receptor antagonist; α-adrenergic receptor antagonist and σ-receptor agonist; phenothiazine antipsychotic. Inhibits glutamate dehydrogenase in vitro. Antipsychotic.
| | Definition | ChEBI: A phenothiazine derivative in which the phenothiazine tricycle carries a chloro substituent at the 2-position and a 3-[4-(2-hydroxyethyl)piperazin-1-yl]propyl group at N-10. | | Manufacturing Process | A mixture of 155 parts of 2-chloro-10-(γ-chloropropyl)phenothiazine, 76 partsof sodium iodide, 216 parts of piperazine and 2,000 parts of butanone is refluxed for 8 hours, concentrated and extracted with dilute hydrochloric acid. The extract is rendered alkaline by addition of dilute potassium carbonate and benzene or chloroform extracted. This extract is washed with water, dried over anhydrous potassium carbonate, filtered and evaporated. Vacuum distillation at 0.1 mm pressure yields 2-chloro-10-[γ-(N-piperazino)propyl]phenothiazine at about 214°-218°C.
A stirred mixture of 5 parts of 2-chloro-10-[γ-(Npiperazino)propyl]phenothiazine, 1.92 parts of 2-bromoethanol, 2.11 parts of potassium carbonate and 35 parts of toluene is refluxed for 5 hours. The mixture is treated with water and benzene and the organic layer is separated, washed with water, dried over anhydrous potassium carbonate, filtered and evaporated. The residue is distilled at about 240°-244°C and 0.15 mm pressure to yield 2-chloro-10-[γ-(N'-β-hydroxyethyl-N-piperazino)propyl]phenothiazine according to US Patent 2,838,507.
The 2-chloro-10-(γ-chloropropyl)phenothiazine starting material is produced from 2-chlorophenothiazine and 1-bromo-3-chloropropane. | | Brand name | Trilafon (Schering). | | Therapeutic Function | Tranquilizer | | General Description | Perphenazine, 4-[3-(2-chlorophenothiazine-10-yl)propyl]piperazineethanol; 2-chloro-10-[3-[4-(2-hydroxyethyl)piperazinyl]propyl]phenothiazine(Trilafon), is an effective antipsychotic and antiemetic. | | Biochem/physiol Actions | D2 dopamine receptor antagonist; α-adrenergic receptor antagonist and σ-receptor agonist; phenothiazine antipsychotic. Inhibits glutamate dehydrogenase in vitro. | | Safety Profile | Poison by ingestion,
intravenous, subcutaneous, intraperitoneal,
and intramuscular routes. Human systemic
effects by intramuscular route: muscle
spasms. Experimental teratogenic and
reproductive effects. Human mutation data
reported. When heated to decomposition it
emits very toxic fumes of SOx, NOx, and
cl-. | | References | 1) Kroeze et al. (2003), H1-Histamine Receptor Affinity Predicts Short-Term Weight Gain for Typical and Atypical Antipsychotic Drugs; Neuropharmacology, 28 519
2) Kornhuber et al. (2011), Identification of Novel Functional Inhibitors of Acid Sphingomyelinase; PLoS One, 6 e23852
3) Kuzu et al. (2017), Modulating cancer cell survival by targeting intracellular cholesterol transport; Br. J. Cancer,?117 513
4) Couee and Tipton (1990), Inhibition of ox brain glutamate by perphenazine; Biochem. Pharmacol. 39 1167 |
| | PERPHENAZINE Preparation Products And Raw materials |
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