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

General Information of Drug (ID: DMY0KGJ)

• Drug Name: Chlorprothixene Drug Info
• Synonyms: Chloroprothixene; Chlorprothixen; Chlorprothixenum; Chlorprothixine; Chlorprotixen; Chlorprotixene; Chlorprotixine; Chlothixen; Clorprotisene; Clorprotixeno; Iaractan; Paxyl; Rentovet; Tactaran; Taractan; Tarasan; Tardan; Traquilan; Trictal; Truxal; Truxaletten; Truxil; Vetacalm; Clorprotisene [DCIT]; MK 184; N 714; N 714C; NCI56378; Alpha-Chlorprothixene; Chlorprothixenum [INN-Latin]; Cis-Chlorprothixene; Clorprotixeno [INN-Spanish]; N-714; Ro 4-0403; Taractan (TN); Truxal (TN); Ro-4-0403;Trans(E)-Chlorprothixen; Chlorprothixene (JAN/USAN/INN); Chlorprothixene [USAN:INN:BAN:JAN]; Cloxan, Taractan, Truxal, Chlorprothixene; Cis-2-Chloro-9-(3-dimethylaminopropylidene)thioxanthene; {3-[2-Chloro-thioxanthen-(9Z)-ylidene]-propyl}-dimethyl-amine; Thioxanthene-delta9,gamma-propylamine, 2-chloro-N,N-dimethyl-, (Z)-(8CI); (3E)-3-(2-chloro-9H-thioxanthen-9-ylidene)-N,N-dimethylpropan-1-amine; (3E)-3-(2-chlorothioxanthen-9-ylidene)-N,N-dimethylpropan-1-amine; (3Z)-3-(2-chloro-9H-thioxanthen-9-ylidene)-N,N-dimethylpropan-1-amine; (3Z)-3-(2-chlorothioxanthen-9-ylidene)-N,N-dimethylpropan-1-amine; (Z)-2-Chloro-9-(omega-dimethylaminopropylidene)thioxanthene; (Z)-2-Chloro-N,N-dimethylthioxanthene-.DELTA.(sup9),(sup.gamma.)-propylamine; (Z)-2-Chloro-N,N-dimethylthioxanthene-delta(sup 9,gamma)-propylamine; (alpha.-2-Chloro-9-.omega.-dimethylamino-propylamine)thioxanthene; 2-Chloro-9-[.omega.-(dimethylamino)propylidene]thioxanthene; 2-Chloro-9-[3-(dimethylamino)propylidene]thioxanthene; 2-Chloro-N,N-dimethylthioxanthene-.delta.(sup 9), .gamma.-propylamine; 3-(2-chloro-9H-thioxanthen-9-ylidene)-N,N-dimethyl-1-propanamine; 3-(2-chloro-9H-thioxanthen-9-ylidene)-N,N-dimethylpropan-1-amine; 3-(2-chlorothioxanthen-9-ylidene)-N,N-dimethylpropan-1-amine

Indication

Disease Entry	ICD 11	Status	REF
Psychotic disorder	6A20-6A25	Approved	[1]

• Therapeutic Class: Antipsychotic Agents
• Cross-matching ID:
  PubChem CID: 667467
  ChEBI ID: CHEBI:50931
  CAS Number: CAS 113-59-7
  TTD Drug ID: DMY0KGJ
  VARIDT Drug ID: DR00591

Molecule-Related Drug Atlas

Drug(s) Targeting Dopamine D2 receptor (D2R)

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

Drug(s) Affected By Prolactin (PRL)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[15]
Ranitidine	DM0GUSX	Gastric ulcer	DA60	Approved	[16]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[17]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[18]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[19]
Thioridazine	DM35M8J	Schizophrenia	6A20	Approved	[20]
Naloxone	DM3FXMA	Narcotic depression	6A7Z	Approved	[21]
Aripiprazole	DM3NUMH	Bipolar I disorder		Approved	[22]
Fluoxetine	DM3PD2C	Bipolar depression		Approved	[23]
Penicillamine	DM40EF6	Cystinuria	5C60.2	Approved	[24]

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	[25]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[26]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[27]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[28]
Clarithromycin	DM4M1SG	Acute maxillary sinusitis		Approved	[28]
Disopyramide	DM5SYZP	Long QT syndrome	BC65.0	Approved	[29]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[30]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[31]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[32]
Flecainide	DMSQDLE	Tachyarrhythmias	BC71	Approved	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

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

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Gene/Protein Processing	[3]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Protein Interaction/Cellular Processes	[4]

References

• [1] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 016149.
• [2] Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics. Bioorg Med Chem Lett. 2009 Jan 15;19(2):538-42.
• [3] 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.
• [4] Pharmacokinetic-pharmacodynamic modeling of tolerance to the prolactin-secreting effect of chlorprothixene after different modes of drug administration. J Pharmacol Exp Ther. 1999 Nov;291(2):547-54.
• [5] 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.
• [6] Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
• [7] CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
• [8] 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.
• [9] Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
• [10] 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).
• [11] Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
• [12] [The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
• [13] 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.
• [14] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [15] Verapamil-induced hyperprolactinemia complicated by a pituitary incidentaloma. Ann Pharmacother. 1995 Oct;29(10):999-1001. doi: 10.1177/106002809502901009.
• [16] [Impotence and gynecomastia secondary to hyperprolactinemia induced by ranitidine]. Therapie. 1994 Jul-Aug;49(4):361-2.
• [17] Differential effects of estrogen receptor antagonists on pituitary lactotroph proliferation and prolactin release. Mol Cell Endocrinol. 2005 Jul 15;239(1-2):27-36. doi: 10.1016/j.mce.2005.04.008.
• [18] Cholinergic modulation of the cerebral metabolic response to citalopram in Alzheimer's disease. Brain. 2009 Feb;132(Pt 2):392-401. doi: 10.1093/brain/awn326. Epub 2009 Jan 19.
• [19] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [20] The effect of thioridazine on prolactinoma growth in a schizophrenic man: case report. Gen Hosp Psychiatry. 1985 Oct;7(4):364-6. doi: 10.1016/0163-8343(85)90053-2.
• [21] Influence of naloxone on muscle sympathetic nerve activity, systemic and calf haemodynamics and ambulatory blood pressure after exercise in mild essential hypertension. J Hypertens. 1995 Apr;13(4):447-61.
• [22] The efficacy, safety, and tolerability of aripiprazole for the treatment of schizoaffective disorder: results from a pooled analysis of a sub-population of subjects from two randomized, double-blind, placebo-controlled, pivotal trials. J Affect Disord. 2009 May;115(1-2):18-26. doi: 10.1016/j.jad.2008.12.017. Epub 2009 Feb 23.
• [23] Serum prolactin levels among outpatients with major depressive disorder during the acute phase of treatment with fluoxetine. J Clin Psychiatry. 2006 Jun;67(6):952-7. doi: 10.4088/jcp.v67n0612.
• [24] Massive breast enlargement in a patient receiving D-penicillamine for systemic sclerosis. J Rheumatol. 1985 Oct;12(5):990-1.
• [25] 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.
• [26] 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.
• [27] 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.
• [28] 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.
• [29] 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.
• [30] 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.
• [31] 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.
• [32] 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.