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.

form 

Solid

pka

pKa 7.8(H2O,t =24±1) (Uncertain)

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)

Safety Information

Hazard Codes 

Xn

Risk Statements 

22-43

Safety Statements 

28-36/37/39-45

RIDADR 

UN 2811 6.1 / PGII

WGK Germany 

3

RTECS 

TL7175000

HS Code 

29349990

Hazardous Substances Data

58-39-9(Hazardous Substances Data)

Toxicity

LD50 oral in rat: 318mg/kg

MSDS

• Language:English Provider:SigmaAldrich

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(58-39-9)Related Product Information

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• Perphenazine maleate,Perphenazine dimaleate