Lofexidine

Summary

Lofexidine (CHEMBL17860) is an approved small-molecule α-adrenergic agonist (ATC N07BC04) targeting ADRA2A, ADRA2B, and ADRA2C; indicated across 7 conditions including drug dependence and opiate dependence.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N07BC04
• Targets: 3 (ADRA2A, ADRA2B, ADRA2C)
• Indications: 7 conditions
• Clinical trials: 25
• Chemistry: 259.13 Da · C11H12Cl2N2O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL17860
Name	Lofexidine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	30668
ChEBI	CHEBI:51368
ATC	N07BC04
Molecular formula	C11H12Cl2N2O
Molecular weight	259.13
InChIKey	KSMAGQUYOIHWFS-UHFFFAOYSA-N

SMILES: CC(C1=NCCN1)OC2=C(C=CC=C2Cl)Cl

IUPAC name: 2-[1-(2,6-dichlorophenoxy)ethyl]-4,5-dihydro-1H-imidazole

Pharmacological roles (ChEBI): α-adrenergic agonist, antihypertensive agent.

Also known as: Lofexidina, Lofexidine, lofexidine, SID170466275, LOFEXIDINE

Parent form; salt/anhydrous children: CHEMBL1788132

Patent coverage: 1,038 distinct patent families (3,777 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
ADRA2A	α2A-adrenoceptor	Agonist	8.36	0.1%	P08913
ADRA2B	α2B-adrenoceptor	Agonist	7.17	0.2%	P18089
ADRA2C	α2C-adrenoceptor	Agonist	7.16	0%	P18825

Broader ChEMBL bioactivity targets: 11 (assay-derived). Sample: Alpha-2A adrenergic receptor, Adrenergic receptor alpha-1, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, Adrenergic receptor alpha-2, 5-hydroxytryptamine receptor 1A, Sodium-dependent serotonin transporter, Alpha-1A adrenergic receptor, Kappa-type opioid receptor, Voltage-gated inwardly rectifying potassium channel KCNH2.

Bioactivity

ChEMBL activities: 19 potent at pChembl ≥ 5 of 21 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ADRA2C	8.86	EC50	1.38	nM	CHEMBL_ACT_8056358
P19328	8.6	IC50	2.5	nM	CHEMBL_ACT_178923
ADRA2A	8.36	Ki	4.37	nM	CHEMBL_ACT_8056273
Q4G017	8.25	Ki	5.62	nM	CHEMBL_ACT_16610442
ADRA2A	8.2	EC50	6.31	nM	CHEMBL_ACT_8056257
ADRA1A	8.15	AC50	7.1	nM	CHEMBL_ACT_25229549
ADRA2A	7.8	AC50	16	nM	CHEMBL_ACT_25220760
ADRA2B	7.17	Ki	67.61	nM	CHEMBL_ACT_8056293
ADRA2C	7.16	Ki	69.18	nM	CHEMBL_ACT_8056313
HTR1A	6.9	Ki	125.9	nM	CHEMBL_ACT_11009777
ADRA2B	6.9	EC50	125.9	nM	CHEMBL_ACT_8056338
ADRA2A	6.89	AC50	130	nM	CHEMBL_ACT_25155848
HTR1A	6.54	AC50	290	nM	CHEMBL_ACT_25164399
ADRA2C	6.38	AC50	420	nM	CHEMBL_ACT_25147534
P15823	6.18	IC50	660	nM	CHEMBL_ACT_178922
ADRA2B	6.13	AC50	740	nM	CHEMBL_ACT_25143369
ADRA1A	6.09	AC50	803.5	nM	CHEMBL_ACT_25137731
HTR1A	5.96	AC50	1100	nM	CHEMBL_ACT_25216695
KCNH2	5.05	AC50	8860	nM	CHEMBL_ACT_25117354

Target pathways

Aggregated over 3 target gene(s): ADRA2A, ADRA2B, ADRA2C.

Top Reactome pathways

19 total, by targets touching each:

Pathway	Targets	Genes
Hemostasis	3	ADRA2A, ADRA2B, ADRA2C
Signal Transduction	3	ADRA2A, ADRA2B, ADRA2C
Signaling by GPCR	3	ADRA2A, ADRA2B, ADRA2C
Class A/1 (Rhodopsin-like receptors)	3	ADRA2A, ADRA2B, ADRA2C
Amine ligand-binding receptors	3	ADRA2A, ADRA2B, ADRA2C
GPCR downstream signalling	3	ADRA2A, ADRA2B, ADRA2C
Adrenoceptors	3	ADRA2A, ADRA2B, ADRA2C
Adrenaline signalling through Alpha-2 adrenergic receptor	3	ADRA2A, ADRA2B, ADRA2C
G alpha (i) signalling events	3	ADRA2A, ADRA2B, ADRA2C
G alpha (z) signalling events	3	ADRA2A, ADRA2B, ADRA2C
GPCR ligand binding	3	ADRA2A, ADRA2B, ADRA2C
Platelet activation, signaling and aggregation	3	ADRA2A, ADRA2B, ADRA2C
Platelet Aggregation (Plug Formation)	3	ADRA2A, ADRA2B, ADRA2C
Metabolism	2	ADRA2A, ADRA2C
Integration of energy metabolism	2	ADRA2A, ADRA2C
Metabolism of proteins	2	ADRA2A, ADRA2C
Adrenaline,noradrenaline inhibits insulin secretion	2	ADRA2A, ADRA2C
Regulation of insulin secretion	2	ADRA2A, ADRA2C
Surfactant metabolism	2	ADRA2A, ADRA2C

Dominant GO biological processes

GO term	Targets
epidermal growth factor receptor signaling pathway	3
G protein-coupled receptor signaling pathway	3
negative regulation of norepinephrine secretion	3
regulation of vasoconstriction	3
platelet activation	3
negative regulation of epinephrine secretion	3
positive regulation of MAPK cascade	3
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	3
adrenergic receptor signaling pathway	3
adenylate cyclase-inhibiting adrenergic receptor signaling pathway	3
regulation of smooth muscle contraction	3
signal transduction	3
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	2
female pregnancy	2
negative regulation of insulin secretion	2

Indications & clinical

Indications

7 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
drug dependence	4	MONDO:0005303	EFO:0003890
opiate dependence	3	MONDO:0005530	EFO:0005611
cannabis dependence	2	MONDO:0005689	EFO:0007191
cocaine dependence	1	MONDO:0005186	EFO:0002610
heroin dependence	1	MONDO:0005367	EFO:0004240
liver failure	1	MONDO:0100192	MONDO:0100192

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 25.

Phase distribution

Phase	Trials
PHASE2	8
PHASE1	8
PHASE4	3
PHASE3	3
PHASE2/PHASE3	2
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01675648	PHASE4	COMPLETED	Lofexidine for Inpatient Opiate Detox in Singapore
NCT04126083	PHASE4	COMPLETED	Lofexidine for Adults Undergoing Lumbar Spine Surgery
NCT05569031	PHASE4	COMPLETED	Treatment of Withdrawal Symptoms and Prevention of Relapse in Patients With Tramadol Abuse
NCT00032942	PHASE3	COMPLETED	Lofexidine for Opiate Withdrawal - 1
NCT00235729	PHASE3	COMPLETED	Lofexidine for Inpatient Opiate Detox
NCT01020019	PHASE2/PHASE3	COMPLETED	Combined Pharmacotherapy for Cannabis Dependency
NCT02363998	PHASE3	COMPLETED	Open-Label, Safety Study of Lofexidine
NCT04325659	PHASE2/PHASE3	COMPLETED	An Innovative Intervention for OUD Treatment
NCT05027919	PHASE2	RECRUITING	Assessing a Clinically-meaningful Opioid Withdrawal Phenotype
NCT05511909	PHASE2	RECRUITING	Evaluating Buspirone to Treat Opioid Withdrawal
NCT00142909	PHASE2	COMPLETED	Effectiveness of Lofexidine to Prevent Stress-Related Opiate Relapse During Naltrexone Treatment - 1
NCT00373503	PHASE2	COMPLETED	Effect of Lofexidine and Oral THC on Marijuana Withdrawal and Relapse
NCT03718065	PHASE2	COMPLETED	Impact of Lofexidine on Stress, Craving and Opioid Use
NCT04056182	PHASE2	COMPLETED	Lofexidine for Management of Opioid Withdrawal With XR-NTX Treatment
NCT04070157	PHASE2	TERMINATED	Randomized, Double-Blind, Placebo-Controlled Pilot Study on the Safety and Effectiveness of LUCEMYRA During an Opioid Taper in Treatment of Withdrawal
NCT04360681	PHASE2	COMPLETED	Lofexidine Combined With Buprenorphine for Reducing Symptoms of PTSD and OU Relapse in Veterans
NCT00000345	PHASE1	COMPLETED	Evaluation of Lofexidine for Treatment of Opiate Withdrawal - 10
NCT00000354	PHASE1	COMPLETED	Evaluation of Lofexidine for Treatment of Opioid Withdrawal - 3
NCT00000358	PHASE1	COMPLETED	Evaluation of Lofexidine for Treatment of Opioid Withdrawal - 7
NCT00218530	PHASE1	COMPLETED	Effectiveness of Naltrexone and Lofexidine in Treating Detoxified Heroin Addicts - 1
NCT01148992	PHASE1	TERMINATED	Interactions Between Intravenous (IV) Cocaine and Lofexidine
NCT02318836	PHASE1	COMPLETED	Single-Dose Pharmacokinetics and Safety of Oral Lofexidine in Hepatically-Impaired Subjects
NCT02446002	PHASE1	COMPLETED	Assessment of the Effect of Naltrexone on Lofexidine Single Dose Pharmacokinetics in Healthy Subjects
NCT02681198	PHASE1	COMPLETED	Lofexidine Pharmacokinetics in the Presence of Paroxetine in Healthy Volunteers
NCT05053503	Not specified	COMPLETED	Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

607 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
ACLIDINIUM BROMIDE	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
Afatinib	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
Almotriptan	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CHENODIOL	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
NAPHAZOLINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
OLANZAPINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
OLODATEROL	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
TAMSULOSIN	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
TEGASEROD	ChEMBL + PubChem	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
ALFUZOSIN	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
AMISULPRIDE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
AMOXAPINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
APOMORPHINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
APRACLONIDINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
ASENAPINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
AZELASTINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BENFLUOREX	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BENPERIDOL	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BENZBROMARONE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BENZQUINAMIDE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BENZTHIAZIDE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BENZTROPINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BITHIONOL	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BRIMONIDINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
BROMPERIDOL	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CABERGOLINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CARIPRAZINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CARVEDILOL	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CHLOROQUINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CINNARIZINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CISAPRIDE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CLEMASTINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CLONIDINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DANAZOL	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DARIFENACIN	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DEXMEDETOMIDINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DOBUTAMINE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DOMPERIDONE	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C
DOTHIEPIN	ChEMBL	Phase 4 (approved)	ADRA2A, ADRA2B, ADRA2C