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
Off-White to Pale Yellow Solid
Trilafon, Schering ,US ,1957
immune suppressant, antifungal
D2 dopamine receptor antagonist; α-adrenergic receptor antagonist and σ-receptor agonist; phenothiazine antipsychotic. Inhibits glutamate dehydrogenase in vitro. Antipsychotic.
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.
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.
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.
D2 dopamine receptor antagonist; α-adrenergic receptor antagonist and σ-receptor agonist; phenothiazine antipsychotic. Inhibits glutamate dehydrogenase in vitro.
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-.
[1] ANDREW J GOUDIE. H1-histamine Receptor Affinity Predicts Short-term Weight Gain for Typical and Atypical Antipsychotic Drugs[J]. Neuropsychopharmacology, 2003, 28 12: 2209-2209. DOI:
10.1038/sj.npp.1300291[2] JOHANNES KORNHUBER. Identification of novel functional inhibitors of acid sphingomyelinase.[J]. ACS Applied Bio Materials, 2011: e23852. DOI:
10.1371/journal.pone.0023852[3] OMER F KUZU. Modulating cancer cell survival by targeting intracellular cholesterol transport[J]. British Journal of Cancer, 2017, 117 4: 513-524. DOI:
10.1038/bjc.2017.200[4] IVAN COUÉE Keith F T. Inhibition of ox brain glutamate dehydrogenase by perphenazine[J]. Biochemical pharmacology, 1990, 39 7: Pages 1167-1173. DOI:
10.1016/0006-2952(90)90258-m
