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| Name | Perphenazine | ||||||||||||||||||||||||||||||||||||
| Accession Number | DB00850 (APRD00429) | ||||||||||||||||||||||||||||||||||||
| Type | small molecule | ||||||||||||||||||||||||||||||||||||
| Groups | approved | ||||||||||||||||||||||||||||||||||||
| Description | An antipsychotic phenothiazine derivative with actions and uses similar to those of chlorpromazine. [PubChem] |
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| Structure |
Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure |
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| CAS number | 58-39-9 | ||||||||||||||||||||||||||||||||||||
| Weight |
Average: 403.969 Monoisotopic: 403.148510866 |
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| Chemical Formula | C21H26ClN3OS | ||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=RGCVKNLCSQQDEP-UHFFFAOYSA-N | ||||||||||||||||||||||||||||||||||||
| InChI |
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
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| IUPAC Name |
2-{4-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]piperazin-1-yl}ethan-1-ol
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| SMILES |
OCCN1CCN(CCCN2C3=C(SC4=C2C=C(Cl)C=C4)C=CC=C3)CC1
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| Mass Spec | show (10 KB) | ||||||||||||||||||||||||||||||||||||
| Taxonomy | |||||||||||||||||||||||||||||||||||||
| Kingdom | Organic | ||||||||||||||||||||||||||||||||||||
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| Pharmacology | |||||||||||||||||||||||||||||||||||||
| Indication | For use in the management of the manifestations of psychotic disorders and for the control of severe nausea and vomiting in adults. | ||||||||||||||||||||||||||||||||||||
| Pharmacodynamics | Perphenazine is a piperazinyl phenothiazine, acts on the central nervous system, and has a greater behavioral potency than other phenothiazine derivatives whose side chains do not contain a piperazine moiety. It is a member of a class of drugs called phenothiazines, which are dopamine D1/D2 receptor antagonists. Perphenazine is 10 to 15 times as potent as chlorpromazine; that means perphenazine is a highly potent antipsychotic. In equivalent doses it has approximately the same frequency and severity of early and late extrapypramidal side-effects compared to Haloperidol. | ||||||||||||||||||||||||||||||||||||
| Mechanism of action | Binds to the dopamine D1 and dopamine D2 receptors and inhibits their activity. The mechanism of the anti-emetic effect is due predominantly to blockage of the dopamine D2 neurotransmitter receptors in the chemoreceptor trigger zone and vomiting centre. Perphenazine also binds the alpha andrenergic receptor. This receptor's action is mediated by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. | ||||||||||||||||||||||||||||||||||||
| Absorption | Absolute bioavailability is 40% following oral administration. | ||||||||||||||||||||||||||||||||||||
| Volume of distribution | Not Available | ||||||||||||||||||||||||||||||||||||
| Protein binding | Not Available | ||||||||||||||||||||||||||||||||||||
| Metabolism |
Hepatic. |
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| Route of elimination | Perphenazine is extensively metabolized in the liver to a number of metabolites by sulfoxidation, hydroxylation, dealkylation, and glucuronidation. | ||||||||||||||||||||||||||||||||||||
| Half life | 8-12 hours, but ranges up to 20 hours. | ||||||||||||||||||||||||||||||||||||
| Clearance | Not Available | ||||||||||||||||||||||||||||||||||||
| Toxicity | Symptoms of overdose include stupor or coma, and children may have convulsive seizures. Signs of arousal may not occur for 48 hours. Oral LD50=318 mg/kg (rat); IPR LD50=64 mg/kg (mouse) | ||||||||||||||||||||||||||||||||||||
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| Pathways | Not Available | ||||||||||||||||||||||||||||||||||||
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| Patents | Not Available | ||||||||||||||||||||||||||||||||||||
| Properties | |||||||||||||||||||||||||||||||||||||
| State | solid | ||||||||||||||||||||||||||||||||||||
| Melting point | 97 oC | ||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Predicted Properties |
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| Synthesis Reference | Not Available | ||||||||||||||||||||||||||||||||||||
| General Reference | Not Available | ||||||||||||||||||||||||||||||||||||
| External Links |
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| ATC Codes |
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| PDB Entries | Not Available | ||||||||||||||||||||||||||||||||||||
| FDA label | show (360.1 KB) | ||||||||||||||||||||||||||||||||||||
| MSDS | show (74.9 KB) | ||||||||||||||||||||||||||||||||||||
| Interactions | |||||||||||||||||||||||||||||||||||||
| Drug Interactions | Not Available | ||||||||||||||||||||||||||||||||||||
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| Targets |
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Pharmacological action: yes
Actions: antagonist This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase Organism class: humanUniProt ID: P14416 ![]() Gene: DRD2 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Pharmacological action: yes
Actions: antagonist This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase Organism class: humanUniProt ID: P21728 ![]() Gene: DRD1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
3. Calmodulin Pharmacological action: unknownActions: inhibitor Calmodulin mediates the control of a large number of enzymes and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases Organism class: humanUniProt ID: P62158 ![]() Gene: CALM1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Enzymes |
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Actions: substrate, inhibitor
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants UniProt ID: P10635![]() Gene: CYP2D6 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate, inhibitor
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen UniProt ID: P05177![]() Gene: CYP1A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics UniProt ID: P20813![]() Gene: CYP2B6 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics UniProt ID: P33260![]() Gene: CYP2C18 ![]() Protein Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine UniProt ID: P33261![]() Gene: CYP2C19 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol) UniProt ID: P10632![]() Gene: CYP2C8 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan UniProt ID: P11712![]() Gene: CYP2C9 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide UniProt ID: P08684![]() Gene: CYP3A4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.