Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C21H26ClN3OS.2C4H4O4 |
| Molecular Weight | 636.113 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 2 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.OCCN1CCN(CCCN2C3=CC=CC=C3SC4=C2C=C(Cl)C=C4)CC1
InChI
InChIKey=HYYMPXVEPSKZOU-SPIKMXEPSA-N
InChI=1S/C21H26ClN3OS.2C4H4O4/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;2*5-3(6)1-2-4(7)8/h1-2,4-7,16,26H,3,8-15H2;2*1-2H,(H,5,6)(H,7,8)/b;2*2-1-
| Molecular Formula | C21H26ClN3OS |
| Molecular Weight | 403.969 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C4H4O4 |
| Molecular Weight | 116.0722 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Optical Activity | NONE |
Perphenazine is a relatively high potency phenothiazine that blocks dopamine 2 receptors predominantly, but also may possess antagonist actions at histamine 1 and cholinergic M1 and alpha 1 adrenergic receptors in the vomiting center leading to reduced nausea and vomiting. The drug was approved by FDA for the treatment of schizophrenia and control of severe nausea and vomiting (either alone or in combination with amitriptyline hydrochloride). Perphenazine is extensively hepatic to metabolites via sulfoxidation, hydroxylation, dealkylation, and glucuronidation; primarily metabolized by CYP2D6 to N-dealkylated perphenazine, perphenazine sulfoxide, and 7-hydroxyperphenazine (active metabolite with 70% of the activity of perphenazine) and excreted in the urine and feces.
CNS Activity
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 8.0 nM [Kd] | |||
| 10.0 nM [Ki] | |||
| 0.16 nM [Ki] | |||
| 1.5 µM [Kd] |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Side-effects of phenothiazines. | 1967 Apr 1 |
|
| Phenothiazines in early labour. | 1967 Feb 11 |
|
| Drug-induced extrapyramidal symptoms: their incidence and treatment. | 1967 Jan |
|
| Oculogyric crises due to phenothiazines. | 1967 Jul 22 |
|
| Perphenazine dystonia presenting as recurrent dislocation of the jaw. | 1969 Jan |
|
| Iatrogenic epilepsy due to antidepressant drugs. | 1969 Oct 11 |
|
| Increased sensitivity to neuroleptics in rats with lesions of the central nervous system. | 1972 |
|
| The mechanism of the potentiating effect of antidepressant drugs on the protective influenc oe of diphenhydramine in experimental catatonia. The role of histamine. | 1974 |
|
| [Psychometric effects of perphenacine below the "neuroleptic threshold" (author's transl)]. | 1975 Dec |
|
| Drug-induced dystonia. | 1975 May |
|
| Asymptomatic idiopathic syndrome of prolonged Q-T interval in a 45-year-old woman. Ventricular tachyarrhythmias precipitated by hypokalemia and therapy with amitriptyline and prephenazine. | 1977 Feb |
|
| Drug-induced anaphylaxis, convulsions, deafness, and extrapyramidal symptoms. | 1977 Mar 12 |
|
| [Acute dystonia in children. 2 cases caused by perphenazine (Trilafon)]. | 1978 Mar 10 |
|
| Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac C capsule. | 1978 Oct 7 |
|
| Electrophysiologic studies of perphenazine and protriptyline in a patient with psychotropic drug-induced ventricular fibrillation. | 1979 Aug |
|
| Seven cases of somnambulism induced by drugs. | 1979 Jul |
|
| Metoclopramide and dystonic reactions in Sardinians. | 1979 Jun 23 |
|
| Pituitary sensitivity to LHRH in hyperprolactinemia induced by perphenazine and renal pituitary transplants in female rats. | 1980 Apr |
|
| Plasma levels of perphenazine (Trilafon) related to development of extrapyramidal side effects. | 1981 |
|
| Actions of clonidine on convulsions and behaviour. | 1981 Jul |
|
| Prolactin and the small intestine. Effect of hyperprolactinaemia on mucosal structure in the rat. | 1981 Jul |
|
| Tricyclic antidepressants and alcoholic blackouts. | 1981 Jun |
|
| Dose-response relationships of perphenazine in the treatment of acute psychoses. | 1982 |
|
| Cerebellar syndrome following neuroleptic induced heat stroke. | 1983 Feb |
|
| Unique sensitivity of Hb Zürich to oxidative injury by phenazopyridine: reversal of the effects by elevating carboxyhemoglobin levels in vivo and in vitro. | 1983 Jun |
|
| Sigma opiates and certain antipsychotic drugs mutually inhibit (+)-[3H] SKF 10,047 and [3H]haloperidol binding in guinea pig brain membranes. | 1984 Sep |
|
| Pharmacology in vivo of the phenylindan derivative, Lu 19-005, a new potent inhibitor of dopamine, noradrenaline and 5-hydroxytryptamine uptake in rat brain. | 1985 Apr |
|
| A case of progressive hemichorea responsive to high-dose reserpine. | 1986 Mar |
|
| Tourette-like syndrome following low dose short-term neuroleptic treatment. | 1986 May |
|
| L-tryptophan in drug-induced movement disorders with insomnia. | 1986 May 8 |
|
| Zuclopenthixol and perphenazine in patients with acute psychotic states. A double-blind multicentre study. | 1987 Jul |
|
| Neuroleptic malignant syndrome during perphenazine treatment. | 1987 Mar |
|
| The relationship between blood perphenazine levels, early resolution of psychotic symptoms, and side effects. | 1990 Aug |
|
| D1/D2 dopamine and N-methyl-D-aspartate (NMDA) receptor participation in experimental catalepsy in rats. | 1992 |
|
| Risperidone versus perphenazine in the treatment of chronic schizophrenic patients with acute exacerbations. | 1993 Dec |
|
| Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. | 1994 Mar |
|
| The efficacy of prophylactic ondansetron, droperidol, perphenazine, and metoclopramide in the prevention of nausea and vomiting after major gynecologic surgery. | 1995 Jul |
|
| BMY-14802 reversed the sigma receptor agonist-induced neck dystonia in rats. | 1996 |
|
| Association of plasma homovanillic acid with behavioral symptoms in patients diagnosed with dementia: a preliminary report. | 1997 Dec 1 |
|
| Induction of mania by risperidone resistant to mood stabilizers. | 1997 Feb |
|
| Olanzapine use in women with antipsychotic-induced hyperprolactinemia. | 1998 Oct |
|
| Perphenazine-induced hiccups. | 1999 Mar |
|
| H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. | 2003 Mar |
|
| Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
|
| Stable expression of constitutively activated mutant h5HT6 and h5HT7 serotonin receptors: inverse agonist activity of antipsychotic drugs. | 2005 May |
|
| [Trazodone for the treatment of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease: a retrospective study focused on the aggression and negativism in caregiving situations]. | 2006 Jun |
|
| Permanent lithium-induced cerebellar toxicity: three cases and review of literature. | 2007 Mar 15 |
|
| BL-1020: a novel antipsychotic drug with GABAergic activity and low catalepsy, is efficacious in a rat model of schizophrenia. | 2009 Jan |
|
| Identification of human Ether-à-go-go related gene modulators by three screening platforms in an academic drug-discovery setting. | 2010 Dec |
|
| Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. | 2011 Jul 14 |
Patents
Sample Use Guides
Moderately disturbed nonhospitalized patients with schizophrenia: 4 to 8 mg t.i.d. initially; reduce as soon as possible to minimum effective dosage. Hospitalized patients with schizophrenia: 8 to 16 mg b.i.d. to q.i.d.; avoid dosages in excess of 64 mg daily. Severe nausea and vomiting in adults: 8 to 16 mg daily in divided doses; 24 mg occasionally may be necessary; early dosage reduction is desirable.
Route of Administration:
Oral
Perphenazine (10-100 microM) was administered, either alone or combined with dopamine, to primary mouse neuronal or intact brain culture and to a human neuroblastoma (NB) cell line (SK-N-SH). Cell viability (measured by neutral red and alamar blue), DNA fragmentation (flow cytometry-NB) were determined. Neuroblastoma: perphenazine decreased viability by 87%.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Tue Oct 22 00:45:32 UTC 2019
by
admin
on
Tue Oct 22 00:45:32 UTC 2019
|
| Record UNII |
7K96LZ09JI
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| Record Status |
Validated (UNII)
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| Record Version |
|
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3534-08-5
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6444477
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SUB03718MIG
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CHEMBL567
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5352-90-9
Created by
admin on Tue Oct 22 00:45:32 UTC 2019 , Edited by admin on Tue Oct 22 00:45:32 UTC 2019
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NON-SPECIFIC STOICHIOMETRY |
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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |