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

General Information of Drug (ID: DM8AI9U)

Drug Name

Loxapine Drug Info

Synonyms

Cloxazepine; Dibenzacepin; Dibenzoazepine; Lossapina; Loxapin; Loxapina; Loxapinsuccinate; Loxapinum; Loxepine; Oxilapine; Lossapina [DCIT]; Loxitane IM; CL 62362; HF 3170; HF3170; Hydrofluoride 3170; LW 3170; S 805; SUM 3170; CL-62362; Loxapac (TN); Loxapina [INN-Spanish]; Loxapinum [INN-Latin]; Loxitane (TN); S-805;SUM-3170; CL-71,563; Loxapine (USAN/INN); Loxapine [USAN:BAN:INN]; Loxapine [USAN:INN:BAN]; 2-Chloro-11-(4-methyl-1-piperazinyl)-dibenz(b,f)(1,4)oxazepine; 2-Chloro-11-(4-methyl-1-piperazinyl)dibenz(b,f)(1,4)oxazepine; 2-Chloro-11-(4-methylpiperazino)dibenzo(b,f)(1,4)oxazepine; 2-chloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine; 8-chloro-6-(4-methylpiperazin-1-yl)benzo[b][1,4]benzoxazepine; 8-chloro-6-(4-methylpiperazin-1-yl)benzo[b][1,5]benzoxazepine

Indication

Disease Entry	ICD 11	Status	REF
Bipolar disorder	6A60	Approved	[1]
Schizophrenia	6A20	Approved	[2]

Therapeutic Class

Antipsychotic Agents

Cross-matching ID

PubChem CID: 3964
ChEBI ID: CHEBI:50841
CAS Number: CAS 1977-10-2
TTD Drug ID: DM8AI9U
INTEDE Drug ID: DR0989
ACDINA Drug ID: D00379

Molecule-Related Drug Atlas

Molecule Type:

DTT

DME

DOT

Drug Status:

Approved Drug(s)

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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]
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Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

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]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[19]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[20]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[21]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[22]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[23]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[17]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[24]
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Drug(s) Metabolized By Cytochrome P450 1A2 (CYP1A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[25]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[26]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[27]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[28]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[29]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[30]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[22]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[31]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[32]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[33]
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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	[34]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[35]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[36]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[20]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[24]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[37]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[38]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[39]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[40]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[41]
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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	[42]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[43]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[44]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[45]
Clarithromycin	DM4M1SG	Acute maxillary sinusitis		Approved	[45]
Disopyramide	DM5SYZP	Long QT syndrome	BC65.0	Approved	[46]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[47]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[48]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[49]
Flecainide	DMSQDLE	Tachyarrhythmias	BC71	Approved	[45]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

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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-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[4]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[4]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[4]

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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	[5]

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References

1	Loxapine FDA Label
2	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
3	Remoxipride in Parkinson's disease: differential response in patients with dyskinesias fluctuations versus psychosis. Clin Neuropharmacol. 1995 Feb;18(1):39-45.
4	In vitro identification of the human cytochrome p450 enzymes involved in the oxidative metabolism of loxapine. Biopharm Drug Dispos. 2011 Oct;32(7):398-407.
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	Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
17	Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
18	Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
19	Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
20	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.
21	Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
22	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
23	The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
24	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.
25	Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
26	Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells. Mol Carcinog. 2004 Jul;40(3):180-8.
27	Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
28	Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
29	PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
30	The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
31	The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
32	Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
33	Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.
34	Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
35	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.
36	CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
37	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.
38	Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
39	Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
40	Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
41	Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
42	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.
43	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.
44	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.
45	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.
46	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.
47	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.
48	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.
49	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.