Details of the Drug-Related molecule(s) Expression Atlas

General Information of Drug (ID: DMA4MRX)

Drug Name

Perphenazine Drug Info

Synonyms

Chlorperphenazine; Chlorpiprazine; Decentan; Emesinal; Etaperazin; Etaperazine; Ethaperazine; Fentazin;PZC; Perfenazina; Perfenazine; Perphenan; Perphenazin; Perphenazinum; Thilatazin; Tranquisan; Trifaron; Trilafon; Trilifan; Triphenot; Perfenazina [Italian]; Perphenazine [Trilafon]; Perphenazine maleate; P 6402; Sch 3940; Apo-Perphenazine; F-mon; Perfenazina [INN-Spanish]; Perphenazinum [INN-Latin]; SCH-3940; Siquil (TN); Triavil (TN); Perphenazine [INN:BAN:JAN]; Perphenazine (JP15/USP/INN); Gamma-[4-(beta-Hydroxyethyl)piperazin-1-yl]propyl-2-chlorophenothiazine; Gamma-(4-(beta-Hydroxyethyl)piperazin-1-yl)propyl-2-chlorophenothiazine; 1',1-(2-Idrossietil)-4,3-(2-cloro-10-fenotiazil)propilpiperazina; 1',1-(2-Idrossietil)-4,3-(2-cloro-10-fenotiazil)propilpiperazina [Italian]; 1-(2-Hydroxyethyl)-4-(3-(2-chloro-10-phenothiazinyl)propyl)piperazine; 1-(2-Hydroxyethyl)-4-[3-(2-chloro-10-phenothiazinyl)propyl]piperazine; 1-Piperazineethanol, 4-[3-(2-chlorophenothiazin-10-yl)propyl]-, trihydrochloride; 2-(4-[3-(2-Chloro-10H-phenothiazin-10-yl)propyl]-1-piperazinyl)ethanol; 2-Chloro-10-(3-(1-(2-hydroxyethyl)-4-piperazinyl)propyl)phenothiazine; 2-Chloro-10-(3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)phenothiazine; 2-Chloro-10-3-(1-(2-hydroxyethyl)-4-piperazinyl)propyl phenothiazine; 2-Chloro-10-3-[1-(2-hydroxyethyl)-4-piperazinyl]propyl phenothiazine; 2-Chloro-10-[3-[4-(2-hydroxyethyl)piperazin-1-yl]propyl]phenothiazine; 2-[4-[3-(2-Chlorophenothiazin-10-yl)propyl]piperazin-1-yl]ethanol;2-{4-[3-(2-Chloro-phenothiazin-10-yl)-propyl]-piperazin-1-yl}-ethanol; 2-{4-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]piperazin-1-yl}ethanol; 4-(3-(2-Chlorophenothiazin-10-yl)propyl)-1-piperazineethanol; 4-[3-(2-Chloro-10H-phenothiazin-10-yl)propyl]-1-piperazineethanol; 4-[3-(2-Chlorophenothiazin-10-yl)propyl]-1-piperazineethanol

Indication

Disease Entry	ICD 11	Status	REF
Schizophrenia	6A20	Approved	[1]
Mixed anxiety and depressive disorder		Investigative	[2]

Therapeutic Class

Antipsychotic Agents

Cross-matching ID

PubChem CID: 4748
ChEBI ID: CHEBI:8028
CAS Number: CAS 58-39-9
TTD Drug ID: DMA4MRX
VARIDT Drug ID: DR00759
INTEDE Drug ID: DR1264
ACDINA Drug ID: D00521

Molecule(s) Related to This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Antagonist	[3]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	Highest Status	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Approved	[4]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Approved	[5]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	Highest Status	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Approved	[6]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Approved	[7]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Approved	[6]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Approved	[6]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Approved	[8]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Approved	[6]
Cytochrome P450 2C18 (CYP2C18)	DEZMWRE	CP2CI_HUMAN	Approved	[6]

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The Expression Level of Molecule(s) in Normal Tissue of Major ADME-Related Organs

Molecule	Molecule Type	Gene Name	Liver	Colon	Kidney	Small Intestine
Dopamine D2 receptor (D2R)	DTT	DRD2	5.345	5.634	5.789	5.901
P-glycoprotein 1 (ABCB1)	DTP	P-GP	7.009	6.988	7.442	8.135
Organic cation transporter 1 (SLC22A1)	DTP	`OCT1	10.261	4.162	4.07	3.797
Cytochrome P450 2C18 (CYP2C18)	DME	CYP2C18	8.485	5.28	4.621	8.889
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	9.791	3.744	3.413	1.609
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	10.036	5.779	6.508	6.481
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	7.867	5.142	5.52	7.08
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	3.307	5.005	3.921	5.327
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	11.76	5.931	6.164	9.423
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	11.692	6.58	4.984	9.089

Molecule Expression Atlas in Normal Tissue of Major ADME-related organs

The Expression Level of Molecule(s) between Disease Section and Healthy Individual Tissue

The Studied Disease

Schizophrenia

ICD Disease Classification

6A20

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Dopamine D2 receptor (D2R)	DTT	DRD2	2.50E-02	-0.08	-0.49
P-glycoprotein 1 (ABCB1)	DTP	P-GP	9.39E-02	1.07E-01	2.80E-01
Organic cation transporter 1 (SLC22A1)	DTP	SLC22A1	8.54E-01	1.24E-02	7.20E-02
Cytochrome P450 2C18 (CYP2C18)	DME	CYP2C18	5.67E-02	2.96E-03	1.50E-02
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	1.82E-04	-1.35E-01	-5.84E-01
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	7.36E-01	1.62E-02	1.08E-01
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	2.40E-01	-3.31E-02	-1.97E-01
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	7.30E-01	-1.91E-02	-1.41E-01
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	1.90E-01	-9.81E-03	-5.96E-02
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.04E-02	6.29E-02	3.54E-01

Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 209).
2	Perphenazine FDA Label
3	CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
4	Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
5	Identification of P-glycoprotein substrates and inhibitors among psychoactive compounds--implications for pharmacokinetics of selected substrates. J Pharm Pharmacol. 2004 Aug;56(8):967-75.
6	Identification of the human cytochrome P450 isoforms mediating in vitro N-dealkylation of perphenazine. Br J Clin Pharmacol. 2000 Dec;50(6):563-71.
7	Use of antidepressant drugs in schizophrenic patients with depression. Encephale. 2006 Mar-Apr;32(2 Pt 1):263-9.
8	Effect of antipsychotic drugs on human liver cytochrome P-450 (CYP) isoforms in vitro: preferential inhibition of CYP2D6. Drug Metab Dispos. 1999 Sep;27(9):1078-84.