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

General Information of Drug (ID: DM1WXA6)

Drug Name

Lofexidine Drug Info

Synonyms

Britlofex; Lofexidina; Lofexidinum; Britlofex (TN); Lofexidina [INN-Spanish]; Lofexidine (INN); Lofexidine [INN:BAN]; Lofexidinum [INN-Latin]; 1H-Imidazole, 2-(1-(2,6-dichlorophenoxy)ethyl)-4,5-dihydro-(9CI); 2-(1-(2,6-Dichlorophenoxy)ethyl)-4,5-dihydro-1H-imidazole; 2-(a-(2,6-dichlorophenoxy)ethyl)2-imidazoline; 2-(alpha-(2,6-Dichlorophenoxy)ethyl)2-imidazoline; 2-(alpha-(2,6-dichlorophenoxy)ethyl) delta-2-imidazoline; 2-[1-(2,6-dichlorophenoxy)ethyl]-4,5-dihydro-1H-imidazole; 2-{1-[(2,6-dichlorophenyl)oxy]ethyl}-4,5-dihydro-1H-imidazole

Indication

Disease Entry	ICD 11	Status	REF
Heroin and opiate withdrawal	6C43	Approved	[1]
Opioid dependence	6C43.2Z	Approved	[2]

Therapeutic Class

Antihypertensive Agents

Cross-matching ID

PubChem CID: 30668
ChEBI ID: CHEBI:51368
CAS Number: CAS 31036-80-3
TTD Drug ID: DM1WXA6
INTEDE Drug ID: DR0967
ACDINA Drug ID: D01217

Molecule-Related Drug Atlas

Molecule Type:

DTT

DME

Drug Status:

Approved Drug(s)

Clinical Trial Drug(s)

Discontinued Drug(s)

Download the Complete Related Drug List

Drug(s) Targeting Adrenergic receptor alpha-2A (ADRA2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MOXONIDINE	DMGFB0E	Alcohol dependence	6C40.2	Approved	[6]
Connexyn	DMF29Q5	Attention deficit hyperactivity disorder	6A05.Z	Approved	[7]
Guanfacine	DMPN5IH	Attention deficit hyperactivity disorder	6A05.Z	Phase 4	[8]
A295	DM55GO2	Aggressive cancer	2A00-2F9Z	IND submitted	[9]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[10]
DSP-1200	DM4WSHG	Depression	6A70-6A7Z	Phase 1	[11]
MAZAPERTINE	DMRHYAU	N. A.	N. A.	Discontinued in Phase 2	[12]
NMI-870	DMU596F	Sexual dysfunction	HA00-HA01	Discontinued in Phase 2	[13]
SNAP-5089	DMROJEN	Heart arrhythmia	BC65	Terminated	[14]
A-80426	DMBC3DG	N. A.	N. A.	Terminated	[15]
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Drug(s) Targeting Adrenergic receptor Alpha-2 (ADRA2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clonidine	DM6RZ9Q	Attention deficit hyperactivity disorder	6A05.Z	Approved	[16]
Meperidine	DMX4GND	Pain	MG30-MG3Z	Approved	[17]
Sodium chloride	DMM3950	Skin burns	ME65.0	Approved	[16]
Guanfacine extended release	DMB1CZ8	Attention deficit hyperactivity disorder	6A05.Z	Approved	[18]
Dexmedetomidine	DM93L4X	Irritability	MB24	Approved	[19]
Yohimbine	DMJCP1Y	Erectile dysfunction	HA01.1	Approved	[20]
Guanabenz	DM5QWEL	High blood pressure	BA00	Approved	[21]
Tizanidine	DMR2IQ4	Spasm	MB47.3	Approved	[22]
Oxymetazoline	DM8ZXT6	Arrhythmia	BC9Z	Approved	[23]
Brimonidine	DMQLT4N	Ocular hypertension	9C61.01	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	[31]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[32]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[33]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[34]
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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	[35]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[36]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[37]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[38]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[39]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[40]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[41]
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[42]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[43]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[44]
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Drug(s) Metabolized By Mephenytoin 4-hydroxylase (CYP2C19)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[45]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[46]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[47]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[48]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[49]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[50]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[51]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[52]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[53]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[54]
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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
Adrenergic receptor Alpha-2 (ADRA2)	TTQ8AFT	NOUNIPROTAC	Agonist	[3]
Adrenergic receptor alpha-2A (ADRA2A)	TTWG9A4	ADA2A_HUMAN	Agonist	[2]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[4]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[4]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[5]

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References

1	A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal. Drug Alcohol Depend. 2008 Sep 1;97(1-2):158-68.
2	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
3	Clinical pharmacokinetics of lofexidine, the alpha 2-adrenergic receptor agonist, in opiate addicts plasma using a highly sensitive liquid chromatography tandem mass spectrometric analysis. Am J DrugAlcohol Abuse. 2008;34(5):611-6.
4	Advisory committee lofexidine hydrochloride (lucemyratm) briefing document.
5	The Drugs.com International Drug Name Database: Lofexidine
6	Synthesis and pharmacologic evaluation of 2-endo-amino-3-exo-isopropylbicyclo[2.2.1]heptane: a potent imidazoline1 receptor specific agent. J Med Chem. 1996 Mar 15;39(6):1193-5.
7	alpha2A-adrenergic receptors heterosynaptically regulate glutamatergic transmission in the bed nucleus of the stria terminalis. Neuroscience. 2009 Sep 29;163(1):339-51.
8	Scientific rationale for the use of alpha2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders. Mol Psychiatry. 2023 Apr 7:1-13.
9	Clinical pipeline report, company report or official report of Klus Pharma
10	A structure-activity relationship study of benzylic modifications of 4-[1-(1-naphthyl)ethyl]-1H-imidazoles on alpha 1- and alpha 2-adrenergic recep... J Med Chem. 1994 Jul 22;37(15):2328-33.
11	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
12	A new arylpiperazine antipsychotic with high D2/D3/5-HT1A/alpha 1A-adrenergic affinity and a low potential for extrapyramidal effects. J Med Chem. 1994 Apr 15;37(8):1060-2.
13	Female Sexual Dysfunction: Therapeutic Options and Experimental Challenges. Cardiovasc Hematol Agents Med Chem. 2009 October; 7(4): 260-269.
14	Design and synthesis of novel dihydropyridine alpha-1a antagonists. Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.
15	Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with alpha2-adrenoceptor blocking... J Med Chem. 2005 Mar 24;48(6):2054-71.
16	Noradrenergic alpha-2 receptor agonists reverse working memory deficits induced by the anxiogenic drug, FG7142, in rats. Pharmacol Biochem Behav. 2000 Nov;67(3):397-403.
17	Meperidine, remifentanil and tramadol but not sufentanil interact with alpha(2)-adrenoceptors in alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptor ... Eur J Pharmacol. 2008 Mar 17;582(1-3):70-7.
18	Emerging drugs for attention-deficit/hyperactivity disorder. Expert Opin Emerg Drugs. 2007 Sep;12(3):423-34.
19	Dexmedetomidine in intensive care unit: a study of hemodynamic changes. Middle East J Anesthesiol. 2002 Oct;16(6):587-95.
20	Acute neurotoxicity after yohimbine ingestion by a body builder. Clin Toxicol (Phila). 2009 Sep;47(8):827-9.
21	Centrally acting sympathetic inhibitors for therapy of patients with hypertension. Nippon Rinsho. 1997 Aug;55(8):2081-5.
22	Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs. 1997 Mar;53(3):435-52.
23	Potent alpha(2A)-adrenoceptor-mediated vasoconstriction by brimonidine in porcine ciliary arteries. Invest Ophthalmol Vis Sci. 2001 Aug;42(9):2049-55.
24	Increased alpha2-adrenergic constriction of isolated arterioles in diffuse scleroderma. Arthritis Rheum. 2000 Aug;43(8):1886-90.
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	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
32	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.
33	Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
34	Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.
35	Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
36	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.
37	CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
38	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.
39	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.
40	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.
41	Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
42	Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
43	Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
44	Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
45	High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
46	Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
47	Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
48	CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
49	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
50	Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
51	Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
52	A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
53	Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
54	Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.