Details
Stereochemistry | ACHIRAL |
Molecular Formula | C21H26ClN3OS |
Molecular Weight | 403.969 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OCCN1CCN(CCCN2C3=CC=CC=C3SC4=CC=C(Cl)C=C24)CC1
InChI
InChIKey=RGCVKNLCSQQDEP-UHFFFAOYSA-N
InChI=1S/C21H26ClN3OS/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
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 |
---|---|---|---|
Target ID: P14416 Gene ID: 1813.0 Gene Symbol: DRD2 Target Organism: Homo sapiens (Human) Sources: http://apm.amegroups.com/article/view/1039/1266 |
0.16 nM [Ki] | ||
Target ID: P35367 Gene ID: 3269.0 Gene Symbol: HRH1 Target Organism: Homo sapiens (Human) Sources: http://apm.amegroups.com/article/view/1039/1266 |
8.0 nM [Kd] | ||
Target ID: P11229 Gene ID: 1128.0 Gene Symbol: CHRM1 Target Organism: Homo sapiens (Human) Sources: http://apm.amegroups.com/article/view/1039/1266 |
1.5 µM [Kd] | ||
Target ID: CHEMBL2094251 Sources: http://apm.amegroups.com/article/view/1039/1266 |
10.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Preventing | PERPHENAZINE Approved UsePerphenazine is indicated for use in the treatment of schizophrenia and for the control of severe nausea and vomiting in adults. Launch Date1988 |
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Preventing | PERPHENAZINE Approved UsePerphenazine is indicated for use in the treatment of schizophrenia and for the control of severe nausea and vomiting in adults. Launch Date1988 |
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Primary | PERPHENAZINE Approved UsePerphenazine is indicated for use in the treatment of schizophrenia and for the control of severe nausea and vomiting in adults. Launch Date1988 |
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Primary | PERPHENAZINE AND AMITRIPTYLINE HYDROCHLORIDE Approved UsePerphenazine and amitriptyline hydrochloride tablets are recommended for treatment of (1) patients with moderate to severe anxiety and/or agitation and depressed mood, (2) patients with depression in whom anxiety and/or agitation are severe, and (3) patients with depression and anxiety in association with chronic physical disease. In many of these patients, anxiety masks the depressive state so that, although therapy with a tranquilizer appears to be indicated, the administration of a tranquilizer alone will not be adequate. Launch Date1988 |
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Primary | PERPHENAZINE AND AMITRIPTYLINE HYDROCHLORIDE Approved UsePerphenazine and amitriptyline hydrochloride tablets are recommended for treatment of (1) patients with moderate to severe anxiety and/or agitation and depressed mood, (2) patients with depression in whom anxiety and/or agitation are severe, and (3) patients with depression and anxiety in association with chronic physical disease. In many of these patients, anxiety masks the depressive state so that, although therapy with a tranquilizer appears to be indicated, the administration of a tranquilizer alone will not be adequate. Launch Date1988 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.546 ng/mL |
16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered: |
PERPHENAZINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
984 pg/mL |
4 mg 3 times / day steady-state, oral dose: 4 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
PERPHENAZINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
509 pg/mL |
4 mg 3 times / day steady-state, oral dose: 4 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
7-HYDROXYPERPHENAZINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
6.673 ng × h/mL |
16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered: |
PERPHENAZINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
9.12 h |
16 mg single, oral dose: 16 mg route of administration: Oral experiment type: SINGLE co-administered: |
PERPHENAZINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
12 h |
4 mg 3 times / day steady-state, oral dose: 4 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
PERPHENAZINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
18.8 h |
4 mg 3 times / day steady-state, oral dose: 4 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
7-HYDROXYPERPHENAZINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
9% |
unknown, unknown |
PERPHENAZINE unknown | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
0.93 g single, oral Overdose |
unhealthy, 42 |
Disc. AE: QT interval prolonged, Hypothermia... AEs leading to discontinuation/dose reduction: QT interval prolonged Sources: Hypothermia Loss of consciousness PR interval prolonged QRS prolonged |
200 mg single, oral Overdose |
unhealthy, 48 |
Disc. AE: Coma, Hypothermia... AEs leading to discontinuation/dose reduction: Coma Sources: Hypothermia Tachycardia Miosis |
30 mg 1 times / day multiple, intramuscular Recommended Dose: 30 mg, 1 times / day Route: intramuscular Route: multiple Dose: 30 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Tardive dyskinesia... AEs leading to discontinuation/dose reduction: Tardive dyskinesia Sources: |
30 mg 1 times / day multiple, intramuscular Recommended Dose: 30 mg, 1 times / day Route: intramuscular Route: multiple Dose: 30 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Neuroleptic malignant syndrome... AEs leading to discontinuation/dose reduction: Neuroleptic malignant syndrome Sources: |
64 mg 1 times / day multiple, oral Recommended Dose: 64 mg, 1 times / day Route: oral Route: multiple Dose: 64 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Tardive dyskinesia... AEs leading to discontinuation/dose reduction: Tardive dyskinesia Sources: |
64 mg 1 times / day multiple, oral Recommended Dose: 64 mg, 1 times / day Route: oral Route: multiple Dose: 64 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Neuroleptic malignant syndrome... AEs leading to discontinuation/dose reduction: Neuroleptic malignant syndrome Sources: |
20 mg single, intramuscular Studied dose Dose: 20 mg Route: intramuscular Route: single Dose: 20 mg Sources: |
unhealthy |
Disc. AE: Neuroleptic malignant syndrome... AEs leading to discontinuation/dose reduction: Neuroleptic malignant syndrome Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Hypothermia | Disc. AE | 0.93 g single, oral Overdose |
unhealthy, 42 |
Loss of consciousness | Disc. AE | 0.93 g single, oral Overdose |
unhealthy, 42 |
PR interval prolonged | Disc. AE | 0.93 g single, oral Overdose |
unhealthy, 42 |
QRS prolonged | Disc. AE | 0.93 g single, oral Overdose |
unhealthy, 42 |
QT interval prolonged | Disc. AE | 0.93 g single, oral Overdose |
unhealthy, 42 |
Coma | Disc. AE | 200 mg single, oral Overdose |
unhealthy, 48 |
Hypothermia | Disc. AE | 200 mg single, oral Overdose |
unhealthy, 48 |
Miosis | Disc. AE | 200 mg single, oral Overdose |
unhealthy, 48 |
Tachycardia | Disc. AE | 200 mg single, oral Overdose |
unhealthy, 48 |
Tardive dyskinesia | Disc. AE | 30 mg 1 times / day multiple, intramuscular Recommended Dose: 30 mg, 1 times / day Route: intramuscular Route: multiple Dose: 30 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Neuroleptic malignant syndrome | Disc. AE | 30 mg 1 times / day multiple, intramuscular Recommended Dose: 30 mg, 1 times / day Route: intramuscular Route: multiple Dose: 30 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Tardive dyskinesia | Disc. AE | 64 mg 1 times / day multiple, oral Recommended Dose: 64 mg, 1 times / day Route: oral Route: multiple Dose: 64 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Neuroleptic malignant syndrome | Disc. AE | 64 mg 1 times / day multiple, oral Recommended Dose: 64 mg, 1 times / day Route: oral Route: multiple Dose: 64 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Neuroleptic malignant syndrome | Disc. AE | 20 mg single, intramuscular Studied dose Dose: 20 mg Route: intramuscular Route: single Dose: 20 mg Sources: |
unhealthy |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/10460810/ Page: abstract |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10460810/ Page: abstract |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10460810/ Page: abstract |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10460810/ Page: abstract |
yes [IC50 1.5 uM] | |||
Page: abstract |
yes [IC50 38.2 uM] | |||
Sources: https://dmd.aspetjournals.org/content/44/3/378.short Page: 42.0 |
yes [IC50 66.2 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10460810/ Page: abstract |
yes [Ki 65.1 uM] | |||
Sources: https://iv.iiarjournals.org/content/23/6/943.short Page: 945.0 |
yes | |||
Page: 962.0 |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 961.0 |
yes | |||
Page: 510.0 |
yes | |||
Page: 961.0 |
yes | |||
Page: 961.0 |
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 1033.0 |
||||
Page: abstract |
PubMed
Title | Date | PubMed |
---|---|---|
Dystonic reaction to perphenazine. | 1969 Aug 9 |
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[Psychometric effects of perphenacine below the "neuroleptic threshold" (author's transl)]. | 1975 Dec |
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Drug-induced dystonia. | 1975 May |
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Tetany, tetanus or drug reaction? A case report. | 1976 Jul |
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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 |
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Drug-induced anaphylaxis, convulsions, deafness, and extrapyramidal symptoms. | 1977 Mar 12 |
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Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac C capsule. | 1978 Oct 7 |
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Metoclopramide and dystonic reactions in Sardinians. | 1979 Jun 23 |
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Toxic psychosis with cimetidine. | 1979 May |
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Actions of clonidine on convulsions and behaviour. | 1981 Jul |
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Prolactin and the small intestine. Effect of hyperprolactinaemia on mucosal structure in the rat. | 1981 Jul |
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Tricyclic antidepressants and alcoholic blackouts. | 1981 Jun |
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GABAergic, dopaminergic and cholinergic interactions in perphenazine-induced catatonia in rats. | 1985 Dec |
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D1/D2 dopamine and N-methyl-D-aspartate (NMDA) receptor participation in experimental catalepsy in rats. | 1992 |
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Risperidone versus perphenazine in the treatment of chronic schizophrenic patients with acute exacerbations. | 1993 Dec |
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Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. | 1994 Mar |
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The efficacy of prophylactic ondansetron, droperidol, perphenazine, and metoclopramide in the prevention of nausea and vomiting after major gynecologic surgery. | 1995 Jul |
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BMY-14802 reversed the sigma receptor agonist-induced neck dystonia in rats. | 1996 |
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Association of plasma homovanillic acid with behavioral symptoms in patients diagnosed with dementia: a preliminary report. | 1997 Dec 1 |
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Induction of mania by risperidone resistant to mood stabilizers. | 1997 Feb |
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Olanzapine use in women with antipsychotic-induced hyperprolactinemia. | 1998 Oct |
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Acquired aplastic anemia secondary to perphenazine. | 1999 Autumn |
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Perphenazine-induced hiccups. | 1999 Mar |
|
[Diabetes mellitus after treatment with clozapine]. | 2000 Feb 26 |
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Antipsychotic-induced extrapyramidal syndromes. Risperidone compared with low- and high-potency conventional antipsychotic drugs. | 2001 Jul |
|
Role of adenosine in drug-induced catatonia in mice. | 2002 Aug |
|
Drug-induced toxic myocarditis. | 2003 |
|
Quercetin potentiates L-Dopa reversal of drug-induced catalepsy in rats: possible COMT/MAO inhibition. | 2003 Jun |
|
H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. | 2003 Mar |
|
Survey on schizophrenia treatment in Mexico: perception and antipsychotic prescription patterns. | 2004 Apr 27 |
|
PASS assisted search and evaluation of some azetidin-2-ones as C.N.S. active agents. | 2005 Aug 3 |
|
Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
|
[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 |
|
Nerve growth factor mRNA expression in the regenerating antler tip of red deer (Cervus elaphus). | 2007 Jan 10 |
|
[Consumption of inappropriate psychotropic drugs in residential homes for the elderly: comparative study between 2001 and 2006]. | 2008 Mar-Apr |
|
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. | 2011 Jul 14 |
|
Selective inhibition of hepatitis C virus infection by hydroxyzine and benztropine. | 2014 Jun |
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12043843
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%.
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Classification Tree | Code System | Code | ||
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NDF-RT |
N0000175746
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WHO-VATC |
QN05AB03
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LIVERTOX |
NBK548366
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NCI_THESAURUS |
C29710
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NDF-RT |
N0000007544
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N0000007544
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N0000007544
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WHO-ATC |
N05AB03
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8076
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637
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SUB09736MIG
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CHEMBL567
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D010546
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FTA7XXY4EZ
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PERPHENAZINE
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C29355
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100000092394
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58-39-9
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200-381-5
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m8567
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3379
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Perphenazine
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209
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)