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

General Information of Drug (ID: DMKYD5N)

Drug Name

Zuclopenthixol Drug Info

Synonyms

Acuphase; CLOPENTHIXOL; Cisordinol; Clopenthixolum; Clopentixol; Clopixol; Zuclopenthixolum; Zuclopentixol; Alpha Clopenthixol; Zuclopenthixolum [Latin]; Zuclopentixol [Spanish]; Acuphase (TN); Alpha-Clopenthixol; Cisordinol (TN); Clopenthixol (USAN); Clopixol (TN); Zuclopenthixol (INN); Zuclopenthixol [BAN:INN]; (Z)-4-(3-(2-Chlorothioxanthen-9-ylidene)propyl)-1-piperazineethanol; 2-[4-[(3Z)-3-(2-chlorothioxanthen-9-ylidene)propyl]piperazin-1-yl]ethanol; 2-{4-[(3Z)-3-(2-chloro-10H-dibenzo[b,e]thiopyran-10-ylidene)propyl]piperazin-1-yl}ethanol; 2-{4-[3-(2-chloro-10H-dibenzo[b,e]thiopyran-10-ylidene)propyl]piperazin-1-yl}ethanol; 4-(3-(2-Chlorothioxanthen-9-ylidene)propyl)-1-piperazineethanol

Indication

Disease Entry	ICD 11	Status	REF
Schizophrenia	6A20	Approved	[1]

Therapeutic Class

Antipsychotic Agents

Cross-matching ID

PubChem CID: 5311507
ChEBI ID: CHEBI:51364
CAS Number: CAS 53772-83-1
TTD Drug ID: DMKYD5N
INTEDE Drug ID: DR1741

Molecule-Related Drug Atlas

Molecule Type:

DTT

DME

DOT

Drug Status:

Approved Drug(s)

Download the Complete Related Drug List

Drug(s) Targeting Dopamine D2 receptor (D2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[6]
Haloperidol	DM96SE0	Delirium		Approved	[7]
Perphenazine	DMA4MRX	Schizophrenia	6A20	Approved	[8]
Perazine	DM2AOTZ	Psychotic disorder	6A20-6A25	Approved	[9]
Domperidone	DMBDPY0	Gastrointestinal disease	DE2Z	Approved	[10]
Levodopa	DMN3E57	Parkinson disease	8A00.0	Approved	[11]
Quetiapine	DM1N62C	Anorexia nervosa cachexia	6B80	Approved	[12]
Pimozide	DMW83TP	Schizophrenia	6A20	Approved	[13]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[14]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[15]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Drug(s) Metabolized By Cytochrome P450 2D6 (CYP2D6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[16]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[17]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[18]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[19]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[21]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[22]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[23]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[24]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[25]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Drug(s) Affected By D(2) dopamine receptor (DRD2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Droperidol	DM0DXA8	Nausea	MD90	Approved	[4]
Thioridazine	DM35M8J	Schizophrenia	6A20	Approved	[4]
Meglitinides	DM1OFHN	Type-2 diabetes	5A11	Approved	[26]
Sulpiride	DMF54ZG	Schizophrenia	6A20	Approved	[27]
Risperidone	DMN6DXL	Bipolar I disorder		Approved	[28]
Olanzapine	DMPFN6Y	Bipolar depression		Approved	[29]
Methamphetamine	DMPM4SK	Anxiety		Approved	[30]
Bromocriptine	DMVE3TK	Acromegaly	5A60.0	Approved	[31]
Fluphenazine	DMIT8LX	Psychotic disorder	6A20-6A25	Approved	[32]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[33]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Drug(s) Affected By Potassium voltage-gated channel subfamily H member 2 (KCNH2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metoclopramide	DMFA5MY	Nausea	MD90	Approved	[34]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[35]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[36]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[37]
Clarithromycin	DM4M1SG	Acute maxillary sinusitis		Approved	[37]
Disopyramide	DM5SYZP	Long QT syndrome	BC65.0	Approved	[38]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[39]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[40]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[41]
Flecainide	DMSQDLE	Tachyarrhythmias	BC71	Approved	[37]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Drug(s) Affected By D(3) dopamine receptor (DRD3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Haloperidol	DM96SE0	Delirium		Approved	[42]
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[43]
Risperidone	DMN6DXL	Bipolar I disorder		Approved	[44]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[45]
Methamphetamine	DMPM4SK	Anxiety		Approved	[46]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[47]
Droperidol	DM0DXA8	Nausea	MD90	Approved	[4]
Thioridazine	DM35M8J	Schizophrenia	6A20	Approved	[4]
Fluphenazine	DMIT8LX	Psychotic disorder	6A20-6A25	Approved	[4]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[4]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Drug(s) Affected By D(4) dopamine receptor (DRD4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[48]
Haloperidol	DM96SE0	Delirium		Approved	[49]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[50]
Niclosamide	DMJAGXQ	Cestodes infection	1F70-1F76	Approved	[51]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[52]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[53]
Methamphetamine	DMPM4SK	Anxiety		Approved	[54]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[55]
Droperidol	DM0DXA8	Nausea	MD90	Approved	[4]
Thioridazine	DM35M8J	Schizophrenia	6A20	Approved	[4]
------------------------------------------------------------------------------------


⏷ Show the Full List of 10 Drug(s)

Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Antagonist	[2]

------------------------------------------------------------------------------------

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6)^{Main DME}	DECB0K3	CP2D6_HUMAN	Substrate	[3]

------------------------------------------------------------------------------------

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
D(2) dopamine receptor (DRD2)	OTBLXKEG	DRD2_HUMAN	Drug Response	[4]
D(3) dopamine receptor (DRD3)	OT0OFFKB	DRD3_HUMAN	Drug Response	[4]
D(4) dopamine receptor (DRD4)	OTAJTO7N	DRD4_HUMAN	Drug Response	[4]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Gene/Protein Processing	[5]

------------------------------------------------------------------------------------

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: 7559).
2	An ethopharmacological assessment of the effects of zuclopenthixol on agonistic interactions in male mice. Methods Find Exp Clin Pharmacol. 1999 Jan-Feb;21(1):11-5.
3	Genotype and co-medication dependent CYP2D6 metabolic activity: effects on serum concentrations of aripiprazole, haloperidol, risperidone, paliperidone and zuclopenthixol. Eur J Clin Pharmacol. 2016 Feb;72(2):175-84.
4	ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
5	Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
6	The Detection of Dopamine Gene Receptors (DRD1-DRD5) Expression on Human Peripheral Blood Lymphocytes by Real Time PCR. Iran J Allergy Asthma Immunol. 2004 Dec;3(4):169-74.
7	Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
8	CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
9	Synthesis and in vitro binding of N-phenyl piperazine analogs as potential dopamine D3 receptor ligands. Bioorg Med Chem. 2005 Jan 3;13(1):77-87.
10	Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
11	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: 3639).
12	Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
13	[The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
14	Modulatory role of dopamine D2 receptors and fundamental role of L-type Ca2+ channels in the induction of long-term potentiation in the basolateral... Eur J Pharmacol. 2009 Mar 15;606(1-3):90-3.
15	Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
16	Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
17	Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
18	CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
19	Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
20	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
21	Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
22	Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
23	Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
24	Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
25	Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
26	Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia. Psychopharmacology (Berl). 2008 Apr;197(2):229-35. doi: 10.1007/s00213-007-1029-z. Epub 2007 Dec 6.
27	Positron emission tomography measurement of dopamine D? receptor occupancy in the pituitary and cerebral cortex: relation to antipsychotic-induced hyperprolactinemia. J Clin Psychiatry. 2010 Sep;71(9):1131-7. doi: 10.4088/JCP.08m04307yel. Epub 2010 Feb 23.
28	Variants of the dopamine D2 receptor gene and risperidone-induced hyperprolactinemia in children and adolescents. Pharmacogenet Genomics. 2009 May;19(5):373-82. doi: 10.1097/FPC.0b013e328329a60f.
29	Dopamine receptor D2 gene is associated with weight gain in schizophrenic patients under long-term atypical antipsychotic treatment. Pharmacogenet Genomics. 2010 Jun;20(6):359-66. doi: 10.1097/FPC.0b013e3283397d06.
30	A preliminary study: novelty seeking, frontal executive function, and dopamine receptor (D2) TaqI A gene polymorphism in patients with methamphetamine dependence. Compr Psychiatry. 2008 Jul-Aug;49(4):387-92. doi: 10.1016/j.comppsych.2008.01.008. Epub 2008 Mar 21.
31	Imaging gene-substance interactions: the effect of the DRD2 TaqIA polymorphism and the dopamine agonist bromocriptine on the brain activation during the anticipation of reward. Neurosci Lett. 2006 Sep 25;405(3):196-201. doi: 10.1016/j.neulet.2006.07.030. Epub 2006 Aug 8.
32	Discovery of antiandrogen activity of nonsteroidal scaffolds of marketed drugs. Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):11927-32. doi: 10.1073/pnas.0609752104. Epub 2007 Jul 2.
33	Response to chlorpromazine treatment may be associated with polymorphisms of the DRD2 gene in Chinese schizophrenic patients. Neurosci Lett. 2005 Mar 7;376(1):1-4. doi: 10.1016/j.neulet.2004.11.014. Epub 2004 Dec 2.
34	Comparison of the effects of metoclopramide and domperidone on HERG channels. Pharmacology. 2005 Apr;74(1):31-6. doi: 10.1159/000083234. Epub 2005 Jan 7.
35	Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG. J Cardiovasc Electrophysiol. 2005 Jan;16(1):54-8. doi: 10.1046/j.1540-8167.2005.04470.x.
36	Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds. Assay Drug Dev Technol. 2004 Oct;2(5):497-506. doi: 10.1089/adt.2004.2.497.
37	Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
38	Pharmacology of the short QT syndrome N588K-hERG K+ channel mutation: differential impact on selected class I and class III antiarrhythmic drugs. Br J Pharmacol. 2008 Nov;155(6):957-66. doi: 10.1038/bjp.2008.325. Epub 2008 Aug 25.
39	Comparison of HERG channel blocking effects of various beta-blockers-- implication for clinical strategy. Br J Pharmacol. 2006 Mar;147(6):642-52. doi: 10.1038/sj.bjp.0706508.
40	Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels. Naunyn Schmiedebergs Arch Pharmacol. 1999 Mar;359(3):212-9. doi: 10.1007/pl00005344.
41	Redox state dependency of HERGS631C channel pharmacology: relation to C-type inactivation. FEBS Lett. 2000 May 26;474(1):111-5. doi: 10.1016/s0014-5793(00)01586-6.
42	The acute EPS of haloperidol may be unrelated to its metabolic transformation to BCPP+. Bioorg Med Chem Lett. 2003 Nov 3;13(21):3779-82. doi: 10.1016/j.bmcl.2003.07.015.
43	Effect of dopamine D3 receptor gene polymorphisms and clozapine treatment response: exploratory analysis of nine polymorphisms and meta-analysis of the Ser9Gly variant. Pharmacogenomics J. 2010 Jun;10(3):200-18. doi: 10.1038/tpj.2009.65. Epub 2009 Dec 22.
44	A common variant in DRD3 gene is associated with risperidone-induced extrapyramidal symptoms. Pharmacogenomics J. 2009 Dec;9(6):404-10. doi: 10.1038/tpj.2009.26. Epub 2009 Jun 9.
45	Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
46	Striatal dopamine d2/d3 receptor availability is reduced in methamphetamine dependence and is linked to impulsivity. J Neurosci. 2009 Nov 25;29(47):14734-40. doi: 10.1523/JNEUROSCI.3765-09.2009.
47	Lower level of endogenous dopamine in patients with cocaine dependence: findings from PET imaging of D(2)/D(3) receptors following acute dopamine depletion. Am J Psychiatry. 2009 Oct;166(10):1170-7. doi: 10.1176/appi.ajp.2009.08121801. Epub 2009 Sep 1.
48	Dopamine D4 receptor gene exon III polymorphism and interindividual variation in response to clozapine. Int J Neurosci. 2005 Nov;115(11):1539-47. doi: 10.1080/00207450590957863.
49	Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95.
50	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
51	Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
52	Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
53	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
54	Association analysis of the DRD4 and COMT genes in methamphetamine abuse. Am J Med Genet B Neuropsychiatr Genet. 2004 Aug 15;129B(1):120-4. doi: 10.1002/ajmg.b.30024.
55	Polymorphisms TaqI A of the DRD2, BalI of the DRD3, exon III repeat of the DRD4, and 3' UTR VNTR of the DAT: association with childhood ADHD in male African-Caribbean cocaine dependents?. Am J Med Genet B Neuropsychiatr Genet. 2007 Dec 5;144B(8):1034-41. doi: 10.1002/ajmg.b.30540.