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Identification
NameLofexidine
Accession NumberDB04948
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionLofexidine is an alpha2-adrenergic receptor agonist. It can be used as a short acting anti-hypertensive, but is mostly used to help relieve symptoms of heroin or opiate withdrawal in opiate dependency. It is approved in the United Kingdom, but is still undergoing clinical trials in the United States.
Structure
Thumb
Synonyms
2-(alpha-(2,6-Dichlorophenoxy)ethyl)2-imidazoline
Lofexidina
Lofexidinum
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BritlofexBritannia
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Lofexidine hydrochloride
Thumb
  • InChI Key: DWWHMKBNNNZGHF-UHFFFAOYNA-N
  • Monoisotopic Mass: 294.009346169
  • Average Mass: 295.593
DBSALT000829
Categories
UNIIUI82K0T627
CAS number31036-80-3
WeightAverage: 259.132
Monoisotopic: 258.03266843
Chemical FormulaC11H12Cl2N2O
InChI KeyKSMAGQUYOIHWFS-UHFFFAOYSA-N
InChI
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)
IUPAC Name
2-[1-(2,6-dichlorophenoxy)ethyl]-4,5-dihydro-1H-imidazole
SMILES
CC(OC1=C(Cl)C=CC=C1Cl)C1=NCCN1
Pharmacology
IndicationInvestigated for use/treatment in addictions and substance abuse.
Structured Indications Not Available
PharmacodynamicsLofexidine is an orally active imidazoline adrenergic alpha-2-receptor agonist; and is believed to have a high affinity for 2A receptor subtypes resulting in less anti-hypertensive activity than clonidine, a non-selective alpha-2-receptor agonist. Hypotension may occur in susceptible subjects, accompanied by a decrease in heart rate. Abrupt discontinuation of lofexidine has been, in some cases, associated with a transient increase in blood pressure to higher than pre-treatment levels. It selectively stimulates receptors in the brain that monitor catecholamine levels in the blood. These receptors close a negative feedback loop that begins with descending sympathetic nerves from the brain that control the production of catecholamines (epinephrine, also known as adrenaline, and norepinephrine) in the adrenal medulla. By fooling the brain into believing that catecholamine levels are higher than they really are, lofexidine causes the brain to reduce its signals to the adrenal medulla, which in turn lowers catecholamine production and blood levels. The result is a lowered heart rate and blood pressure. This central action is responsible for the suppression of opiate withdrawal symptoms.
Mechanism of actionLofexidine is an alpha2-adrenergic receptor agonist.
TargetKindPharmacological actionActionsOrganismUniProt ID
Alpha-2A adrenergic receptorProteinyes
agonist
HumanP08913 details
Related Articles
AbsorptionLofexidine is extensively absorbed and achieves peak plasma concentration at 3 hours after administration of a single dose. Bioavailability is over 90% following oral administration.
Volume of distributionNot Available
Protein binding80 to 90%
Metabolism

Lofexidine undergoes extensive metabolism in the liver and excretion is mainly by the kidney.

Route of eliminationNot Available
Half life11 hours
ClearanceNot Available
ToxicityLofexidine was tolerated at high dosage in singe dose toxicity studies in animals, the LD50 being >77 mg/kg. With repeat dosing in mice, rats and dogs symptoms related to the pharmacology of the drug (ataxia, sedation, tremor, unkempt appearance and exhaustion) appeared. Overdosage may cause hypotension, bradycardia and sedation.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE may increase the hypotensive activities of Lofexidine.Experimental
AcebutololLofexidine may increase the atrioventricular blocking (AV block) activities of Acebutolol.Approved
AcetazolamideThe risk or severity of adverse effects can be increased when Lofexidine is combined with Acetazolamide.Approved, Vet Approved
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Lofexidine.Approved
AlfuzosinAlfuzosin may increase the hypotensive activities of Lofexidine.Approved, Investigational
AliskirenLofexidine may increase the hypotensive activities of Aliskiren.Approved, Investigational
AlprenololLofexidine may increase the atrioventricular blocking (AV block) activities of Alprenolol.Approved, Withdrawn
AmbrisentanLofexidine may increase the hypotensive activities of Ambrisentan.Approved, Investigational
AmifostineLofexidine may increase the hypotensive activities of Amifostine.Approved, Investigational
AmilorideThe risk or severity of adverse effects can be increased when Amiloride is combined with Lofexidine.Approved
AmineptineAmineptine may decrease the antihypertensive activities of Lofexidine.Illicit, Withdrawn
AmiodaroneThe risk or severity of adverse effects can be increased when Amiodarone is combined with Lofexidine.Approved, Investigational
AmitriptylineAmitriptyline may decrease the antihypertensive activities of Lofexidine.Approved
AmlodipineAmlodipine may increase the hypotensive activities of Lofexidine.Approved
AmobarbitalAmobarbital may increase the hypotensive activities of Lofexidine.Approved, Illicit
Amphotericin BThe risk or severity of adverse effects can be increased when Amphotericin B is combined with Lofexidine.Approved, Investigational
Amyl NitriteThe risk or severity of adverse effects can be increased when Amyl Nitrite is combined with Lofexidine.Approved
Aop200704Lofexidine may increase the atrioventricular blocking (AV block) activities of Aop200704.Investigational
ApomorphineThe risk or severity of adverse effects can be increased when Apomorphine is combined with Lofexidine.Approved, Investigational
ApraclonidineThe risk or severity of adverse effects can be increased when Apraclonidine is combined with Lofexidine.Approved
AripiprazoleAripiprazole may increase the hypotensive activities of Lofexidine.Approved, Investigational
ArotinololLofexidine may increase the atrioventricular blocking (AV block) activities of Arotinolol.Approved
Arsenic trioxideThe risk or severity of adverse effects can be increased when Arsenic trioxide is combined with Lofexidine.Approved, Investigational
AtenololLofexidine may increase the atrioventricular blocking (AV block) activities of Atenolol.Approved
Azilsartan medoxomilThe risk or severity of adverse effects can be increased when Azilsartan medoxomil is combined with Lofexidine.Approved
BarbexacloneBarbexaclone may increase the hypotensive activities of Lofexidine.Experimental
BarbitalBarbital may increase the hypotensive activities of Lofexidine.Illicit
BarnidipineThe risk or severity of adverse effects can be increased when Barnidipine is combined with Lofexidine.Approved
BefunololLofexidine may increase the atrioventricular blocking (AV block) activities of Befunolol.Experimental
BenazeprilBenazepril may increase the hypotensive activities of Lofexidine.Approved, Investigational
BendroflumethiazideBendroflumethiazide may increase the hypotensive activities of Lofexidine.Approved
BenmoxinBenmoxin may increase the hypotensive activities of Lofexidine.Withdrawn
Benzylpenicilloyl PolylysineLofexidine may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BepridilBepridil may increase the hypotensive activities of Lofexidine.Approved, Withdrawn
BetaxololLofexidine may increase the atrioventricular blocking (AV block) activities of Betaxolol.Approved
BethanidineBethanidine may increase the hypotensive activities of Lofexidine.Approved
BevantololLofexidine may increase the atrioventricular blocking (AV block) activities of Bevantolol.Approved
BimatoprostBimatoprost may increase the hypotensive activities of Lofexidine.Approved, Investigational
BisoprololLofexidine may increase the atrioventricular blocking (AV block) activities of Bisoprolol.Approved
BopindololLofexidine may increase the atrioventricular blocking (AV block) activities of Bopindolol.Approved
BortezomibThe risk or severity of adverse effects can be increased when Bortezomib is combined with Lofexidine.Approved, Investigational
BosentanBosentan may increase the hypotensive activities of Lofexidine.Approved, Investigational
BretyliumBretylium may increase the hypotensive activities of Lofexidine.Approved
BrimonidineBrimonidine may increase the hypotensive activities of Lofexidine.Approved
BrimonidineBrimonidine may increase the antihypertensive activities of Lofexidine.Approved
BromocriptineBromocriptine may increase the hypertensive activities of Lofexidine.Approved, Investigational
BucindololLofexidine may increase the atrioventricular blocking (AV block) activities of Bucindolol.Investigational
BufuralolLofexidine may increase the atrioventricular blocking (AV block) activities of Bufuralol.Experimental, Investigational
BumetanideThe risk or severity of adverse effects can be increased when Bumetanide is combined with Lofexidine.Approved
BupivacaineThe risk or severity of adverse effects can be increased when Bupivacaine is combined with Lofexidine.Approved, Investigational
BupranololLofexidine may increase the atrioventricular blocking (AV block) activities of Bupranolol.Approved
CabergolineCabergoline may increase the hypertensive activities of Lofexidine.Approved
CanagliflozinThe risk or severity of adverse effects can be increased when Canagliflozin is combined with Lofexidine.Approved
CandesartanCandesartan may increase the hypotensive activities of Lofexidine.Approved
CandoxatrilCandoxatril may increase the hypotensive activities of Lofexidine.Experimental
CaptoprilCaptopril may increase the hypotensive activities of Lofexidine.Approved
CarbetocinThe risk or severity of adverse effects can be increased when Carbetocin is combined with Lofexidine.Approved
CaroxazoneCaroxazone may increase the hypotensive activities of Lofexidine.Withdrawn
CarteololLofexidine may increase the atrioventricular blocking (AV block) activities of Carteolol.Approved
CarvedilolLofexidine may increase the atrioventricular blocking (AV block) activities of Carvedilol.Approved, Investigational
CeliprololLofexidine may increase the atrioventricular blocking (AV block) activities of Celiprolol.Approved, Investigational
ChlorothiazideChlorothiazide may increase the hypotensive activities of Lofexidine.Approved, Vet Approved
ChlorpromazineThe risk or severity of adverse effects can be increased when Chlorpromazine is combined with Lofexidine.Approved, Vet Approved
ChlorthalidoneChlorthalidone may increase the hypotensive activities of Lofexidine.Approved
CilazaprilCilazapril may increase the hypotensive activities of Lofexidine.Approved
CilnidipineThe risk or severity of adverse effects can be increased when Cilnidipine is combined with Lofexidine.Approved
ClevidipineThe risk or severity of adverse effects can be increased when Clevidipine is combined with Lofexidine.Approved
ClofarabineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Lofexidine.Approved, Investigational
ClomipramineClomipramine may decrease the antihypertensive activities of Lofexidine.Approved, Vet Approved
ClonidineClonidine may increase the hypotensive activities of Lofexidine.Approved
ClozapineThe risk or severity of adverse effects can be increased when Clozapine is combined with Lofexidine.Approved
ConivaptanThe risk or severity of adverse effects can be increased when Conivaptan is combined with Lofexidine.Approved, Investigational
CryptenamineCryptenamine may increase the hypotensive activities of Lofexidine.Approved
CyclobenzaprineCyclobenzaprine may decrease the antihypertensive activities of Lofexidine.Approved
CyclothiazideCyclothiazide may increase the hypotensive activities of Lofexidine.Approved
DapagliflozinThe risk or severity of adverse effects can be increased when Dapagliflozin is combined with Lofexidine.Approved
DebrisoquinDebrisoquin may increase the hypotensive activities of Lofexidine.Approved
DeserpidineLofexidine may increase the hypotensive activities of Deserpidine.Approved
DesfluraneThe risk or severity of adverse effects can be increased when Desflurane is combined with Lofexidine.Approved
DesipramineDesipramine may decrease the antihypertensive activities of Lofexidine.Approved
DesvenlafaxineDesvenlafaxine may increase the tachycardic activities of Lofexidine.Approved
DexmedetomidineThe risk or severity of adverse effects can be increased when Dexmedetomidine is combined with Lofexidine.Approved, Vet Approved
DiazoxideDiazoxide may increase the hypotensive activities of Lofexidine.Approved
DiclofenamideThe risk or severity of adverse effects can be increased when Diclofenamide is combined with Lofexidine.Approved
DihydralazineLofexidine may increase the hypotensive activities of Dihydralazine.Investigational
DihydroergotamineDihydroergotamine may increase the hypertensive activities of Lofexidine.Approved
DiltiazemDiltiazem may increase the hypotensive activities of Lofexidine.Approved
DinutuximabThe risk or severity of adverse effects can be increased when Dinutuximab is combined with Lofexidine.Approved
DipyridamoleThe risk or severity of adverse effects can be increased when Dipyridamole is combined with Lofexidine.Approved
DorzolamideDorzolamide may increase the hypotensive activities of Lofexidine.Approved
DosulepinDosulepin may decrease the antihypertensive activities of Lofexidine.Approved
DoxazosinDoxazosin may increase the hypotensive activities of Lofexidine.Approved
DoxepinDoxepin may decrease the antihypertensive activities of Lofexidine.Approved
DuloxetineLofexidine may increase the orthostatic hypotensive activities of Duloxetine.Approved
EfonidipineLofexidine may increase the hypotensive activities of Efonidipine.Approved
EmpagliflozinThe risk or severity of adverse effects can be increased when Empagliflozin is combined with Lofexidine.Approved
EnalaprilEnalapril may increase the hypotensive activities of Lofexidine.Approved, Vet Approved
EnalaprilatLofexidine may increase the hypotensive activities of Enalaprilat.Approved
EplerenoneThe risk or severity of adverse effects can be increased when Eplerenone is combined with Lofexidine.Approved
EpoprostenolEpoprostenol may increase the hypotensive activities of Lofexidine.Approved
EprosartanEprosartan may increase the hypotensive activities of Lofexidine.Approved
Ergoloid mesylateErgoloid mesylate may increase the hypertensive activities of Lofexidine.Approved
ErgonovineErgonovine may increase the hypertensive activities of Lofexidine.Approved
ErgotamineErgotamine may increase the hypertensive activities of Lofexidine.Approved
EsmirtazapineEsmirtazapine may decrease the antihypertensive activities of Lofexidine.Investigational
EsmololLofexidine may increase the atrioventricular blocking (AV block) activities of Esmolol.Approved
Etacrynic acidThe risk or severity of adverse effects can be increased when Etacrynic acid is combined with Lofexidine.Approved
FelodipineFelodipine may increase the hypotensive activities of Lofexidine.Approved, Investigational
FenoldopamFenoldopam may increase the hypotensive activities of Lofexidine.Approved
FimasartanThe risk or severity of adverse effects can be increased when Fimasartan is combined with Lofexidine.Approved
FosinoprilFosinopril may increase the hypotensive activities of Lofexidine.Approved
FurazolidoneFurazolidone may increase the hypotensive activities of Lofexidine.Approved, Vet Approved
FurosemideThe risk or severity of adverse effects can be increased when Furosemide is combined with Lofexidine.Approved, Vet Approved
GuanabenzGuanabenz may increase the hypotensive activities of Lofexidine.Approved
GuanadrelGuanadrel may increase the hypotensive activities of Lofexidine.Approved
GuanethidineGuanethidine may increase the hypotensive activities of Lofexidine.Approved
GuanfacineGuanfacine may increase the hypotensive activities of Lofexidine.Approved, Investigational
HalothaneThe risk or severity of adverse effects can be increased when Halothane is combined with Lofexidine.Approved, Vet Approved
HexamethoniumLofexidine may increase the hypotensive activities of Hexamethonium.Experimental
HexobarbitalHexobarbital may increase the hypotensive activities of Lofexidine.Approved
HyaluronidaseHyaluronidase may increase the vasoconstricting activities of Lofexidine.Approved, Investigational
HydracarbazineHydracarbazine may increase the hypotensive activities of Lofexidine.Approved
HydralazineHydralazine may increase the hypotensive activities of Lofexidine.Approved
HydrochlorothiazideHydrochlorothiazide may increase the hypotensive activities of Lofexidine.Approved, Vet Approved
HydroflumethiazideHydroflumethiazide may increase the hypotensive activities of Lofexidine.Approved
IloprostIloprost may increase the hypotensive activities of Lofexidine.Approved, Investigational
ImidaprilThe risk or severity of adverse effects can be increased when Imidapril is combined with Lofexidine.Investigational
ImipramineImipramine may decrease the antihypertensive activities of Lofexidine.Approved
IndapamideIndapamide may increase the hypotensive activities of Lofexidine.Approved
IndenololLofexidine may increase the atrioventricular blocking (AV block) activities of Indenolol.Withdrawn
IndoraminLofexidine may increase the hypotensive activities of Indoramin.Withdrawn
IobenguaneThe therapeutic efficacy of Iobenguane can be decreased when used in combination with Lofexidine.Approved
IproclozideIproclozide may increase the hypotensive activities of Lofexidine.Withdrawn
IproniazidIproniazid may increase the hypotensive activities of Lofexidine.Withdrawn
IrbesartanIrbesartan may increase the hypotensive activities of Lofexidine.Approved, Investigational
IsocarboxazidIsocarboxazid may increase the hypotensive activities of Lofexidine.Approved
IsofluraneThe risk or severity of adverse effects can be increased when Isoflurane is combined with Lofexidine.Approved, Vet Approved
Isosorbide DinitrateThe risk or severity of adverse effects can be increased when Isosorbide Dinitrate is combined with Lofexidine.Approved
Isosorbide MononitrateThe risk or severity of adverse effects can be increased when Isosorbide Mononitrate is combined with Lofexidine.Approved
IsoxsuprineThe risk or severity of adverse effects can be increased when Isoxsuprine is combined with Lofexidine.Approved, Withdrawn
IsradipineIsradipine may increase the hypotensive activities of Lofexidine.Approved
KetanserinLofexidine may increase the hypotensive activities of Ketanserin.Investigational
LabetalolLofexidine may increase the atrioventricular blocking (AV block) activities of Labetalol.Approved
LacidipineLofexidine may increase the hypotensive activities of Lacidipine.Approved
LatanoprostLatanoprost may increase the hypotensive activities of Lofexidine.Approved, Investigational
LercanidipineLercanidipine may increase the hypotensive activities of Lofexidine.Approved, Investigational
LevobunololThe risk or severity of adverse effects can be increased when Levobunolol is combined with Lofexidine.Approved
LevobupivacaineThe risk or severity of adverse effects can be increased when Levobupivacaine is combined with Lofexidine.Approved
LevodopaLofexidine may increase the orthostatic hypotensive activities of Levodopa.Approved
LevomilnacipranLevomilnacipran may increase the tachycardic activities of Lofexidine.Approved
LevosimendanThe risk or severity of adverse effects can be increased when Levosimendan is combined with Lofexidine.Approved, Investigational
LisinoprilLisinopril may increase the hypotensive activities of Lofexidine.Approved, Investigational
LosartanLosartan may increase the hypotensive activities of Lofexidine.Approved
MacitentanLofexidine may increase the hypotensive activities of Macitentan.Approved
ManidipineLofexidine may increase the hypotensive activities of Manidipine.Approved
MannitolThe risk or severity of adverse effects can be increased when Mannitol is combined with Lofexidine.Approved, Investigational
MebanazineMebanazine may increase the hypotensive activities of Lofexidine.Withdrawn
MecamylamineMecamylamine may increase the hypotensive activities of Lofexidine.Approved
MethazolamideThe risk or severity of adverse effects can be increased when Methazolamide is combined with Lofexidine.Approved
MethohexitalMethohexital may increase the hypotensive activities of Lofexidine.Approved
MethyclothiazideThe risk or severity of adverse effects can be increased when Methyclothiazide is combined with Lofexidine.Approved
MethyldopaMethyldopa may increase the hypotensive activities of Lofexidine.Approved
Methylene blueMethylene blue may increase the hypotensive activities of Lofexidine.Investigational
MethylnaltrexoneThe risk or severity of adverse effects can be increased when Methylnaltrexone is combined with Lofexidine.Approved
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Lofexidine.Approved, Investigational
MethylphenobarbitalMethylphenobarbital may increase the hypotensive activities of Lofexidine.Approved
MetipranololMetipranolol may increase the hypotensive activities of Lofexidine.Approved
MetolazoneMetolazone may increase the hypotensive activities of Lofexidine.Approved
MetoprololLofexidine may increase the atrioventricular blocking (AV block) activities of Metoprolol.Approved, Investigational
MetyrosineLofexidine may increase the hypotensive activities of Metyrosine.Approved
MianserinThe therapeutic efficacy of Lofexidine can be decreased when used in combination with Mianserin.Approved
MibefradilMibefradil may increase the hypotensive activities of Lofexidine.Withdrawn
MilnacipranMilnacipran may increase the tachycardic activities of Lofexidine.Approved
MinaprineMinaprine may increase the hypotensive activities of Lofexidine.Approved
MinoxidilMinoxidil may increase the hypotensive activities of Lofexidine.Approved
MirtazapineMirtazapine may decrease the antihypertensive activities of Lofexidine.Approved
MoclobemideMoclobemide may increase the hypotensive activities of Lofexidine.Approved
MoexiprilMoexipril may increase the hypotensive activities of Lofexidine.Approved
MolsidomineMolsidomine may increase the hypotensive activities of Lofexidine.Approved
MorphineThe risk or severity of adverse effects can be increased when Lofexidine is combined with Morphine.Approved, Investigational
MoxonidineLofexidine may increase the hypotensive activities of Moxonidine.Approved
NabiloneThe risk or severity of adverse effects can be increased when Lofexidine is combined with Nabilone.Approved, Investigational
NadololLofexidine may increase the atrioventricular blocking (AV block) activities of Nadolol.Approved
NaftopidilLofexidine may increase the hypotensive activities of Naftopidil.Investigational
NaloxegolThe risk or severity of adverse effects can be increased when Lofexidine is combined with Naloxegol.Approved
NebivololNebivolol may increase the hypotensive activities of Lofexidine.Approved, Investigational
NesiritideThe risk or severity of adverse effects can be increased when Nesiritide is combined with Lofexidine.Approved, Investigational
NialamideNialamide may increase the hypotensive activities of Lofexidine.Withdrawn
NicardipineNicardipine may increase the hypotensive activities of Lofexidine.Approved
NicorandilNicorandil may increase the hypotensive activities of Lofexidine.Approved
NifedipineThe risk or severity of adverse effects can be increased when Nifedipine is combined with Lofexidine.Approved
NiguldipineLofexidine may increase the hypotensive activities of Niguldipine.Experimental
NilvadipineLofexidine may increase the hypotensive activities of Nilvadipine.Approved
NimodipineNimodipine may increase the hypotensive activities of Lofexidine.Approved
NisoldipineNisoldipine may increase the hypotensive activities of Lofexidine.Approved
NitrendipineNitrendipine may increase the hypotensive activities of Lofexidine.Approved
Nitric OxideThe risk or severity of adverse effects can be increased when Lofexidine is combined with Nitric Oxide.Approved
NitroglycerinThe risk or severity of adverse effects can be increased when Nitroglycerin is combined with Lofexidine.Approved, Investigational
NitroprussideNitroprusside may increase the hypotensive activities of Lofexidine.Approved
NortriptylineNortriptyline may decrease the antihypertensive activities of Lofexidine.Approved
ObinutuzumabLofexidine may increase the hypotensive activities of Obinutuzumab.Approved
OctamoxinOctamoxin may increase the hypotensive activities of Lofexidine.Withdrawn
OlmesartanOlmesartan may increase the hypotensive activities of Lofexidine.Approved, Investigational
OmapatrilatOmapatrilat may increase the hypotensive activities of Lofexidine.Investigational
OpipramolOpipramol may decrease the antihypertensive activities of Lofexidine.Investigational
OxprenololLofexidine may increase the atrioventricular blocking (AV block) activities of Oxprenolol.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Lofexidine is combined with Paclitaxel.Approved, Vet Approved
PapaverineThe risk or severity of adverse effects can be increased when Papaverine is combined with Lofexidine.Approved
PargylinePargyline may increase the hypotensive activities of Lofexidine.Approved
PenbutololLofexidine may increase the atrioventricular blocking (AV block) activities of Penbutolol.Approved, Investigational
PentobarbitalPentobarbital may increase the hypotensive activities of Lofexidine.Approved, Vet Approved
PentoliniumPentolinium may increase the hypotensive activities of Lofexidine.Approved
PentoxifyllinePentoxifylline may increase the hypotensive activities of Lofexidine.Approved, Investigational
PerindoprilPerindopril may increase the hypotensive activities of Lofexidine.Approved
PhenelzinePhenelzine may increase the hypotensive activities of Lofexidine.Approved
PheniprazinePheniprazine may increase the hypotensive activities of Lofexidine.Withdrawn
PhenobarbitalPhenobarbital may increase the hypotensive activities of Lofexidine.Approved
PhenoxybenzaminePhenoxybenzamine may increase the hypotensive activities of Lofexidine.Approved
PhenoxypropazinePhenoxypropazine may increase the hypotensive activities of Lofexidine.Withdrawn
PhentolaminePhentolamine may increase the hypotensive activities of Lofexidine.Approved
PinacidilLofexidine may increase the hypotensive activities of Pinacidil.Withdrawn
PindololLofexidine may increase the atrioventricular blocking (AV block) activities of Pindolol.Approved
PipamperoneThe risk or severity of adverse effects can be increased when Lofexidine is combined with Pipamperone.Approved
PirlindolePirlindole may increase the hypotensive activities of Lofexidine.Approved
PivhydrazinePivhydrazine may increase the hypotensive activities of Lofexidine.Withdrawn
PolythiazidePolythiazide may increase the hypotensive activities of Lofexidine.Approved
PractololLofexidine may increase the atrioventricular blocking (AV block) activities of Practolol.Approved
PramipexoleThe risk or severity of adverse effects can be increased when Lofexidine is combined with Pramipexole.Approved, Investigational
PrazosinPrazosin may increase the hypotensive activities of Lofexidine.Approved
PrimidonePrimidone may increase the hypotensive activities of Lofexidine.Approved, Vet Approved
PropofolThe risk or severity of adverse effects can be increased when Lofexidine is combined with Propofol.Approved, Investigational, Vet Approved
PropranololLofexidine may increase the atrioventricular blocking (AV block) activities of Propranolol.Approved, Investigational
ProtriptylineProtriptyline may decrease the antihypertensive activities of Lofexidine.Approved
QuetiapineThe risk or severity of adverse effects can be increased when Quetiapine is combined with Lofexidine.Approved
QuinaprilQuinapril may increase the hypotensive activities of Lofexidine.Approved, Investigational
QuinineQuinine may increase the hypotensive activities of Lofexidine.Approved
RamiprilRamipril may increase the hypotensive activities of Lofexidine.Approved
RasagilineRasagiline may increase the hypotensive activities of Lofexidine.Approved
RemifentanilThe risk or severity of adverse effects can be increased when Lofexidine is combined with Remifentanil.Approved
RemikirenRemikiren may increase the hypotensive activities of Lofexidine.Approved
RescinnamineLofexidine may increase the hypotensive activities of Rescinnamine.Approved
ReserpineReserpine may increase the hypotensive activities of Lofexidine.Approved
RilmenidineLofexidine may increase the hypotensive activities of Rilmenidine.Investigational
RiociguatLofexidine may increase the hypotensive activities of Riociguat.Approved
RisperidoneLofexidine may increase the hypotensive activities of Risperidone.Approved, Investigational
RituximabLofexidine may increase the hypotensive activities of Rituximab.Approved
RopiniroleThe risk or severity of adverse effects can be increased when Lofexidine is combined with Ropinirole.Approved, Investigational
RopivacaineThe risk or severity of adverse effects can be increased when Lofexidine is combined with Ropivacaine.Approved
RotigotineThe risk or severity of adverse effects can be increased when Lofexidine is combined with Rotigotine.Approved
SacubitrilThe risk or severity of adverse effects can be increased when Lofexidine is combined with Sacubitril.Approved
SafrazineSafrazine may increase the hypotensive activities of Lofexidine.Withdrawn
SaprisartanSaprisartan may increase the hypotensive activities of Lofexidine.Experimental
SecobarbitalSecobarbital may increase the hypotensive activities of Lofexidine.Approved, Vet Approved
SelegilineSelegiline may increase the hypotensive activities of Lofexidine.Approved, Investigational, Vet Approved
SelexipagLofexidine may increase the hypotensive activities of Selexipag.Approved
SevofluraneThe risk or severity of adverse effects can be increased when Lofexidine is combined with Sevoflurane.Approved, Vet Approved
SildenafilSildenafil may increase the antihypertensive activities of Lofexidine.Approved, Investigational
SilodosinSilodosin may decrease the vasoconstricting activities of Lofexidine.Approved
SitaxentanLofexidine may increase the hypotensive activities of Sitaxentan.Approved, Investigational, Withdrawn
Sodium NitriteThe risk or severity of adverse effects can be increased when Lofexidine is combined with Sodium Nitrite.Approved
SotalolLofexidine may increase the atrioventricular blocking (AV block) activities of Sotalol.Approved
SpiraprilSpirapril may increase the hypotensive activities of Lofexidine.Approved
SpironolactoneSpironolactone may decrease the vasoconstricting activities of Lofexidine.Approved
StreptokinaseThe risk or severity of adverse effects can be increased when Lofexidine is combined with Streptokinase.Approved
SufentanilThe risk or severity of adverse effects can be increased when Lofexidine is combined with Sufentanil.Approved, Investigational
TadalafilTadalafil may increase the antihypertensive activities of Lofexidine.Approved, Investigational
TamsulosinThe risk or severity of adverse effects can be increased when Lofexidine is combined with Tamsulosin.Approved, Investigational
TelmisartanTelmisartan may increase the hypotensive activities of Lofexidine.Approved, Investigational
TemocaprilLofexidine may increase the hypotensive activities of Temocapril.Experimental, Investigational
TerazosinThe risk or severity of adverse effects can be increased when Terazosin is combined with Lofexidine.Approved
TerlipressinTerlipressin may increase the hypotensive activities of Lofexidine.Approved, Investigational
ThalidomideThe risk or severity of adverse effects can be increased when Lofexidine is combined with Thalidomide.Approved, Investigational, Withdrawn
ThiamylalThiamylal may increase the hypotensive activities of Lofexidine.Approved, Vet Approved
ThiopentalThiopental may increase the hypotensive activities of Lofexidine.Approved, Vet Approved
ThioridazineThe risk or severity of adverse effects can be increased when Lofexidine is combined with Thioridazine.Approved
TianeptineTianeptine may decrease the antihypertensive activities of Lofexidine.Approved
TiboloneLofexidine may increase the hypotensive activities of Tibolone.Approved
TicrynafenTicrynafen may increase the hypotensive activities of Lofexidine.Withdrawn
TimololLofexidine may increase the atrioventricular blocking (AV block) activities of Timolol.Approved
TizanidineThe risk or severity of adverse effects can be increased when Tizanidine is combined with Lofexidine.Approved
TolazolineTolazoline may increase the hypotensive activities of Lofexidine.Approved, Vet Approved
TolcaponeThe risk or severity of adverse effects can be increased when Lofexidine is combined with Tolcapone.Approved, Withdrawn
ToloxatoneToloxatone may increase the hypotensive activities of Lofexidine.Approved
TorasemideTorasemide may increase the hypotensive activities of Lofexidine.Approved
TrandolaprilTrandolapril may increase the hypotensive activities of Lofexidine.Approved
Trans-2-PhenylcyclopropylamineTrans-2-Phenylcyclopropylamine may increase the hypotensive activities of Lofexidine.Experimental
TranylcypromineTranylcypromine may increase the hypotensive activities of Lofexidine.Approved
TravoprostTravoprost may increase the hypotensive activities of Lofexidine.Approved
TreprostinilTreprostinil may increase the hypotensive activities of Lofexidine.Approved, Investigational
TretinoinThe risk or severity of adverse effects can be increased when Lofexidine is combined with Tretinoin.Approved, Investigational, Nutraceutical
TriamtereneThe risk or severity of adverse effects can be increased when Triamterene is combined with Lofexidine.Approved
TrichlormethiazideTrichlormethiazide may increase the hypotensive activities of Lofexidine.Approved, Vet Approved
TrimazosinLofexidine may increase the hypotensive activities of Trimazosin.Experimental
TrimethaphanTrimethaphan may increase the hypotensive activities of Lofexidine.Approved
TrimipramineTrimipramine may decrease the antihypertensive activities of Lofexidine.Approved
UdenafilUdenafil may increase the antihypertensive activities of Lofexidine.Approved, Investigational
UnoprostoneLofexidine may increase the hypotensive activities of Unoprostone.Approved
ValsartanValsartan may increase the hypotensive activities of Lofexidine.Approved, Investigational
VardenafilVardenafil may increase the antihypertensive activities of Lofexidine.Approved
VenlafaxineVenlafaxine may increase the tachycardic activities of Lofexidine.Approved
VerapamilThe risk or severity of adverse effects can be increased when Verapamil is combined with Lofexidine.Approved
VinpocetineLofexidine may increase the hypotensive activities of Vinpocetine.Investigational
XylometazolineLofexidine may increase the hypotensive activities of Xylometazoline.Approved
YohimbineYohimbine may decrease the antihypertensive activities of Lofexidine.Approved, Vet Approved
Food InteractionsNot Available
References
Synthesis Reference

U.S. Patent 3,966,757.

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 ]
External Links
ATC CodesN07BC04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9969
Blood Brain Barrier+0.9582
Caco-2 permeable+0.539
P-glycoprotein substrateSubstrate0.7119
P-glycoprotein inhibitor INon-inhibitor0.9326
P-glycoprotein inhibitor IINon-inhibitor0.8089
Renal organic cation transporterInhibitor0.6897
CYP450 2C9 substrateNon-substrate0.744
CYP450 2D6 substrateNon-substrate0.6421
CYP450 3A4 substrateNon-substrate0.5055
CYP450 1A2 substrateInhibitor0.8023
CYP450 2C9 inhibitorNon-inhibitor0.739
CYP450 2D6 inhibitorInhibitor0.6616
CYP450 2C19 inhibitorNon-inhibitor0.6593
CYP450 3A4 inhibitorNon-inhibitor0.9304
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5075
Ames testNon AMES toxic0.7322
CarcinogenicityNon-carcinogens0.913
BiodegradationNot ready biodegradable0.996
Rat acute toxicity2.9567 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6244
hERG inhibition (predictor II)Non-inhibitor0.7293
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point221-223U.S. Patent 3,966,757.
Predicted Properties
PropertyValueSource
Water Solubility0.147 mg/mLALOGPS
logP3.31ALOGPS
logP2.66ChemAxon
logS-3.2ALOGPS
pKa (Strongest Basic)7.67ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area33.62 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity64.41 m3·mol-1ChemAxon
Polarizability25.11 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenol ethers
Direct ParentPhenol ethers
Alternative Parents
Substituents
  • Phenol ether
  • 1,3-dichlorobenzene
  • Halobenzene
  • Chlorobenzene
  • Alkyl aryl ether
  • Imidolactam
  • Aryl halide
  • Aryl chloride
  • 2-imidazoline
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Ether
  • Carboxylic acid amidine
  • Amidine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Thioesterase binding
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 = mianser...
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular Weight:
48956.275 Da
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 ]
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Drug created on October 21, 2007 16:23 / Updated on August 17, 2016 12:24