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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2021-09-14 15:00:47 UTC
HMDB IDHMDB0015606
Secondary Accession Numbers
  • HMDB15606
Metabolite Identification
Common NameLofexidine
DescriptionLofexidine, also known as britlofex, belongs to the class of organic compounds known as dichlorobenzenes. Dichlorobenzenes are compounds containing a benzene with exactly two chlorine atoms attached to it. These enzymes catalyze the hydroxylation of lofexidine and the opening of imidazoline ring to form N-(2-aminoethyl)-2-(2,6-dichlorophenoxy)propanamide. Lofexidine is a very strong basic compound (based on its pKa). In clinical trials, lofexidine presented more severe opioid withdrawal effects than observed with methadone. This will generate an increase in norepinephrine which is associated with the symptoms of withdrawal. This metabolite is deamidated and forms 2-(2,6-dichlorophenoxy) propionic acid and 2,6-dichlorophenol.
Structure
Data?1582753315
Synonyms
ValueSource
2-(alpha-(2,6-Dichlorophenoxy)ethyl)2-imidazolineChEBI
LofexidinaChEBI
LofexidinumChEBI
2-(a-(2,6-Dichlorophenoxy)ethyl)2-imidazolineGenerator
2-(Α-(2,6-dichlorophenoxy)ethyl)2-imidazolineGenerator
2-(1-(2,6-Dichlorophenoxy)ethyl)-4,5-dihydro-1H-imidazoleHMDB
BritLofexHMDB
2-(alpha-(2,6-Dichlorophenoxy)ethyl) delta-2-imidazolineHMDB
Lofexidine mono-hydrochlorideHMDB
Lofexidine, (+-)-isomerHMDB
Lofexidine hydrochlorideHMDB
Lofexidine monohydrochlorideHMDB
Chemical FormulaC11H12Cl2N2O
Average Molecular Weight259.132
Monoisotopic Molecular Weight258.03266843
IUPAC Name2-[1-(2,6-dichlorophenoxy)ethyl]-4,5-dihydro-1H-imidazole
Traditional Namelofexidine
CAS Registry Number31036-80-3
SMILES
CC(OC1=C(Cl)C=CC=C1Cl)C1=NCCN1
InChI Identifier
InChI=1S/C11H12Cl2N2O/c1-7(11-14-5-6-15-11)16-10-8(12)3-2-4-9(10)13/h2-4,7H,5-6H2,1H3,(H,14,15)
InChI KeyKSMAGQUYOIHWFS-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as dichlorobenzenes. Dichlorobenzenes are compounds containing a benzene with exactly two chlorine atoms attached to it.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassHalobenzenes
Direct ParentDichlorobenzenes
Alternative Parents
Substituents
  • Phenoxy compound
  • 1,3-dichlorobenzene
  • Phenol ether
  • Alkyl aryl ether
  • Aryl chloride
  • Aryl halide
  • Imidolactam
  • 2-imidazoline
  • Amidine
  • Carboxylic acid amidine
  • Ether
  • Azacycle
  • Organoheterocyclic compound
  • Carboximidamide
  • Propargyl-type 1,3-dipolar organic compound
  • Organic 1,3-dipolar compound
  • Organic oxygen compound
  • Organohalogen compound
  • Organochloride
  • Organonitrogen compound
  • Organooxygen compound
  • Organopnictogen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Disposition

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point127 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.15 g/LNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.15 g/LALOGPS
logP3.31ALOGPS
logP2.66ChemAxon
logS-3.2ALOGPS
pKa (Strongest Basic)7.67ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area33.62 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity64.41 m³·mol⁻¹ChemAxon
Polarizability25.11 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra

GC-MS

Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0459-8910000000-1ef99e126c03b06d18c02017-09-01View Spectrum
MSMass Spectrum (Electron Ionization)splash10-0459-8910000000-1ef99e126c03b06d18c02021-09-05View Spectrum

LC-MS/MS

Spectrum TypeDescriptionSplash KeyDeposition DateView
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0bta-5090000000-966c69c881b261c7d39d2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0bta-5090000000-966c69c881b261c7d39d2017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-1090000000-8e8a68e1e0da6f2db6c02016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-9320000000-7faea52073b41d21462b2016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9200000000-3304f31e8314347b14f62016-08-02View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-1190000000-551a9882c5776e0755892016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0bt9-1590000000-6c7abe970b6a82a66fb12016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-03k9-5900000000-6009a76b4783970c379f2016-08-03View Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB04948 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB04948 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB04948
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID28460
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkLofexidine
METLIN IDNot Available
PubChem Compound30668
PDB IDNot Available
ChEBI ID51368
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Walsh SL, Strain EC, Bigelow GE: Evaluation of the effects of lofexidine and clonidine on naloxone-precipitated withdrawal in opioid-dependent humans. Addiction. 2003 Apr;98(4):427-39. [PubMed:12653813 ]
  2. Manufacturer Website [Link]

Enzymes

General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular weight:
48956.3
References
  1. Jin Y, Verstappen A, Elko E, Cammarata P, Yorio T: Effects of lofexidine, an alpha 2-adrenoreceptor agonist, on ocular blood flow and ion transport of rabbit iris-ciliary body. J Ocul Pharmacol. 1992 Spring;8(1):23-33. [PubMed:1357064 ]
  2. Strang J, Bearn J, Gossop M: Lofexidine for opiate detoxification: review of recent randomised and open controlled trials. Am J Addict. 1999 Fall;8(4):337-48. [PubMed:10598217 ]
  3. Erb S, Hitchcott PK, Rajabi H, Mueller D, Shaham Y, Stewart J: Alpha-2 adrenergic receptor agonists block stress-induced reinstatement of cocaine seeking. Neuropsychopharmacology. 2000 Aug;23(2):138-50. [PubMed:10882840 ]