Identification

Name
Lofexidine
Accession Number
DB04948
Type
Small Molecule
Groups
Approved, Investigational
Description

Lofexidine 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
Product Ingredients
IngredientUNIICASInChI Key
Lofexidine hydrochlorideV47G1SDI1B21498-08-8DWWHMKBNNNZGHF-UHFFFAOYSA-N
International/Other Brands
Britlofex (Britannia)
Categories
UNII
UI82K0T627
CAS number
31036-80-3
Weight
Average: 259.132
Monoisotopic: 258.03266843
Chemical Formula
C11H12Cl2N2O
InChI Key
KSMAGQUYOIHWFS-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

Indication

Investigated for use/treatment in addictions and substance abuse.

Structured Indications
Not Available
Pharmacodynamics

Lofexidine 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 action

Lofexidine is an alpha2-adrenergic receptor agonist.

TargetActionsOrganism
AAlpha-2A adrenergic receptor
agonist
Human
Absorption

Lofexidine 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 distribution
Not Available
Protein binding

80 to 90%

Metabolism

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

Route of elimination
Not Available
Half life

11 hours

Clearance
Not Available
Toxicity

Lofexidine 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not 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
AldesleukinThe risk or severity of adverse effects can be increased when Lofexidine is combined with Aldesleukin.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 Lofexidine is combined with Amiloride.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
AmoxapineAmoxapine may decrease the antihypertensive activities of Lofexidine.Approved
AmphetamineAmphetamine 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 Lofexidine is combined with Amyl Nitrite.Approved
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 Lofexidine is combined with Apraclonidine.Approved
AripiprazoleAripiprazole may increase the hypotensive activities of Lofexidine.Approved, Investigational
ArotinololLofexidine may increase the atrioventricular blocking (AV block) activities of Arotinolol.Approved, Investigational
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
AvanafilAvanafil may increase the antihypertensive activities of Lofexidine.Approved
Azilsartan medoxomilThe risk or severity of adverse effects can be increased when Lofexidine is combined with Azilsartan medoxomil.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
BietaserpineBietaserpine may increase the hypotensive activities of Lofexidine.Experimental
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
BQ-123Lofexidine may increase the hypotensive activities of BQ-123.Investigational
BretyliumBretylium may increase the hypotensive activities of Lofexidine.Approved
BrimonidineBrimonidine may increase the antihypertensive activities of Lofexidine.Approved
BrofaromineBrofaromine may increase the hypotensive activities of Lofexidine.Experimental
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with 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 Lofexidine is combined with Bumetanide.Approved
BunazosinBunazosin may decrease the vasoconstricting activities of Lofexidine.Investigational
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
CadralazineCadralazine may increase the hypotensive activities of Lofexidine.Experimental
CafedrineLofexidine may increase the hypotensive activities of Cafedrine.Investigational
CanagliflozinThe risk or severity of adverse effects can be increased when Lofexidine is combined with Canagliflozin.Approved
CandesartanLofexidine may increase the hypotensive activities of Candesartan.Experimental
Candesartan cilexetilCandesartan cilexetil 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
CicletanineLofexidine may increase the hypotensive activities of Cicletanine.Investigational
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, Investigational
ClevidipineThe risk or severity of adverse effects can be increased when Lofexidine is combined with Clevidipine.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
CloranololLofexidine may increase the atrioventricular blocking (AV block) activities of Cloranolol.Experimental
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
CyclopenthiazideLofexidine may increase the hypotensive activities of Cyclopenthiazide.Experimental
CyclothiazideCyclothiazide may increase the hypotensive activities of Lofexidine.Approved
DapagliflozinThe risk or severity of adverse effects can be increased when Lofexidine is combined with Dapagliflozin.Approved
DebrisoquinDebrisoquin may increase the hypotensive activities of Lofexidine.Approved, Investigational
DelaprilLofexidine may increase the hypotensive activities of Delapril.Experimental
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 Lofexidine is combined with Dexmedetomidine.Approved, Vet Approved
DiazoxideDiazoxide may increase the hypotensive activities of Lofexidine.Approved
DibenzepinDibenzepin may decrease the antihypertensive activities of Lofexidine.Experimental
DiclofenamideThe risk or severity of adverse effects can be increased when Lofexidine is combined with Diclofenamide.Approved
diethylnorspermineLofexidine may increase the hypotensive activities of diethylnorspermine.Investigational
DihydralazineDihydralazine may increase the hypotensive activities of Lofexidine.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 Lofexidine is combined with Dinutuximab.Approved
DipyridamoleThe risk or severity of adverse effects can be increased when Lofexidine is combined with Dipyridamole.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, Investigational
EmpagliflozinThe risk or severity of adverse effects can be increased when Lofexidine is combined with Empagliflozin.Approved
EnalaprilEnalapril may increase the hypotensive activities of Lofexidine.Approved, Vet Approved
EnalaprilatLofexidine may increase the hypotensive activities of Enalaprilat.Approved
EndralazineEndralazine may increase the hypotensive activities of Lofexidine.Experimental
EpanololLofexidine may increase the atrioventricular blocking (AV block) activities of Epanolol.Experimental
EplerenoneThe risk or severity of adverse effects can be increased when Lofexidine is combined with Eplerenone.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 Lofexidine is combined with Etacrynic acid.Approved
FelodipineFelodipine may increase the hypotensive activities of Lofexidine.Approved, Investigational
FenoldopamFenoldopam may increase the hypotensive activities of Lofexidine.Approved
Ferulic acidLofexidine may increase the hypotensive activities of Ferulic acid.Experimental
FimasartanThe risk or severity of adverse effects can be increased when Fimasartan is combined with Lofexidine.Approved, Investigational
FosinoprilFosinopril may increase the hypotensive activities of Lofexidine.Approved
FurazolidoneFurazolidone may increase the hypotensive activities of Lofexidine.Approved, Investigational, Vet Approved
FurosemideThe risk or severity of adverse effects can be increased when Lofexidine is combined with Furosemide.Approved, Vet Approved
GuanabenzGuanabenz may increase the hypotensive activities of Lofexidine.Approved, Investigational
GuanadrelGuanadrel may increase the hypotensive activities of Lofexidine.Approved
GuanazodineLofexidine may increase the hypotensive activities of Guanazodine.Experimental
GuanethidineGuanethidine may increase the hypotensive activities of Lofexidine.Approved
GuanfacineGuanfacine may increase the hypotensive activities of Lofexidine.Approved, Investigational
GuanoclorLofexidine may increase the hypotensive activities of Guanoclor.Experimental
GuanoxabenzLofexidine may increase the hypotensive activities of Guanoxabenz.Experimental
GuanoxanLofexidine may increase the hypotensive activities of Guanoxan.Experimental
HalothaneThe risk or severity of adverse effects can be increased when Halothane is combined with Lofexidine.Approved, Vet Approved
HarmalineHarmaline may increase the hypotensive activities of Lofexidine.Experimental
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.Experimental
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, Investigational
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
IndoraminIndoramin may increase the hypotensive activities of Lofexidine.Withdrawn
IobenguaneThe therapeutic efficacy of Iobenguane can be decreased when used in combination with Lofexidine.Approved, Investigational
IprindoleIprindole may decrease the antihypertensive activities of Lofexidine.Experimental
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 Lofexidine is combined with Isosorbide Dinitrate.Approved
Isosorbide MononitrateThe risk or severity of adverse effects can be increased when Lofexidine is combined with Isosorbide Mononitrate.Approved
IsoxsuprineThe risk or severity of adverse effects can be increased when Lofexidine is combined with Isoxsuprine.Approved, Withdrawn
IsradipineIsradipine may increase the hypotensive activities of Lofexidine.Approved
KetanserinKetanserin may increase the hypotensive activities of Lofexidine.Investigational
LabetalolLofexidine may increase the atrioventricular blocking (AV block) activities of Labetalol.Approved
LacidipineLofexidine may increase the hypotensive activities of Lacidipine.Approved, Investigational
LandiololLofexidine may increase the atrioventricular blocking (AV block) activities of Landiolol.Investigational
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 Lofexidine is combined with Levobunolol.Approved
LevobupivacaineThe risk or severity of adverse effects can be increased when Levobupivacaine is combined with Lofexidine.Approved, Investigational
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
LinsidomineLofexidine may increase the hypotensive activities of Linsidomine.Experimental
LisinoprilLisinopril may increase the hypotensive activities of Lofexidine.Approved, Investigational
LofepramineLofepramine may decrease the antihypertensive activities of Lofexidine.Experimental
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, Investigational
MannitolThe risk or severity of adverse effects can be increased when Lofexidine is combined with Mannitol.Approved, Investigational
MebanazineMebanazine may increase the hypotensive activities of Lofexidine.Withdrawn
MecamylamineMecamylamine may increase the hypotensive activities of Lofexidine.Approved
MepindololLofexidine may increase the atrioventricular blocking (AV block) activities of Mepindolol.Experimental
MethazolamideThe risk or severity of adverse effects can be increased when Lofexidine is combined with Methazolamide.Approved
MethohexitalMethohexital may increase the hypotensive activities of Lofexidine.Approved
MethoserpidineLofexidine may increase the hypotensive activities of Methoserpidine.Experimental
MethyclothiazideThe risk or severity of adverse effects can be increased when Lofexidine is combined with Methyclothiazide.Approved
MethyldopaMethyldopa may increase the hypotensive activities of Lofexidine.Approved
Methylene blueMethylene blue may increase the hypotensive activities of Lofexidine.Approved, Investigational
MethylergometrineMethylergometrine may increase the hypertensive activities of Lofexidine.Approved
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, Investigational
MibefradilMibefradil may increase the hypotensive activities of Lofexidine.Investigational, 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
MirodenafilMirodenafil may increase the antihypertensive activities of Lofexidine.Investigational
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, Investigational
MorphineThe risk or severity of adverse effects can be increased when Lofexidine is combined with Morphine.Approved, Investigational
MoxonidineMoxonidine may increase the hypotensive activities of Lofexidine.Approved, Investigational
MuzolimineLofexidine may increase the hypotensive activities of Muzolimine.Experimental
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
NebivololLofexidine may increase the atrioventricular blocking (AV block) activities of Nebivolol.Approved, Investigational
NesiritideThe risk or severity of adverse effects can be increased when Lofexidine is combined with Nesiritide.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, Investigational
NifedipineThe risk or severity of adverse effects can be increased when Lofexidine is combined with Nifedipine.Approved
NiguldipineLofexidine may increase the hypotensive activities of Niguldipine.Experimental
NilvadipineLofexidine may increase the hypotensive activities of Nilvadipine.Approved, Investigational
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, Investigational
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 Lofexidine is combined with Nitroglycerin.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 Lofexidine is combined with Papaverine.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
PinacidilPinacidil may increase the hypotensive activities of Lofexidine.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, Investigational
PirlindolePirlindole may increase the hypotensive activities of Lofexidine.Approved
PivhydrazinePivhydrazine may increase the hypotensive activities of Lofexidine.Withdrawn
Platelet Activating FactorLofexidine may increase the atrioventricular blocking (AV block) activities of Platelet Activating Factor.Experimental
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
ProcarbazineProcarbazine may increase the hypotensive activities of Lofexidine.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 Lofexidine is combined with Quetiapine.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, Investigational
RilmenidineRilmenidine may increase the hypotensive activities of Lofexidine.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, Investigational
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
TalinololLofexidine may increase the atrioventricular blocking (AV block) activities of Talinolol.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 Lofexidine is combined with Terazosin.Approved
TerlipressinTerlipressin may increase the hypotensive activities of Lofexidine.Approved, Investigational
TertatololLofexidine may increase the atrioventricular blocking (AV block) activities of Tertatolol.Experimental
TetrahydropalmatineLofexidine may increase the hypotensive activities of Tetrahydropalmatine.Investigational
ThalidomideThe risk or severity of adverse effects can be increased when Lofexidine is combined with Thalidomide.Approved, Investigational, Withdrawn
TheodrenalineLofexidine may increase the hypotensive activities of Theodrenaline.Investigational
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, Withdrawn
TianeptineTianeptine may decrease the antihypertensive activities of Lofexidine.Approved, Investigational
TiboloneLofexidine may increase the hypotensive activities of Tibolone.Approved, Investigational
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 Lofexidine is combined with Tizanidine.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
TolonidineLofexidine may increase the hypotensive activities of Tolonidine.Experimental
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 Lofexidine is combined with Triamterene.Approved
TrichlormethiazideTrichlormethiazide may increase the hypotensive activities of Lofexidine.Approved, Vet Approved
TrimazosinTrimazosin may increase the hypotensive activities of Lofexidine.Experimental
TrimethaphanTrimethaphan may increase the hypotensive activities of Lofexidine.Approved, Investigational
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
UrapidilUrapidil may decrease the vasoconstricting activities of Lofexidine.Investigational
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 Lofexidine is combined with Verapamil.Approved
VincamineLofexidine may increase the hypotensive activities of Vincamine.Experimental
VinpocetineLofexidine may increase the hypotensive activities of Vinpocetine.Investigational
XipamideLofexidine may increase the hypotensive activities of Xipamide.Experimental
XylometazolineLofexidine may increase the hypotensive activities of Xylometazoline.Approved
YohimbineYohimbine may decrease the antihypertensive activities of Lofexidine.Approved, Vet Approved
ZofenoprilLofexidine may increase the hypotensive activities of Zofenopril.Experimental
Food Interactions
Not 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
Human Metabolome Database
HMDB15606
PubChem Compound
30668
PubChem Substance
46508453
ChemSpider
28460
BindingDB
50019646
ChEBI
51368
ChEMBL
CHEMBL17860
Therapeutic Targets Database
DAP000064
PharmGKB
PA164744510
Wikipedia
Lofexidine
ATC Codes
N07BC04 — Lofexidine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic ScienceNormal Healthy Volunteers1
1CompletedBasic ScienceNormal Healthy Volunteers Will be Treated With Lofexidine to Understand the Absolute Bioavailability and Mass Balance Recovery of the Product / Normal Healthy Volunteers Will be Treated With Lofexidine to Understand the Absolute Bioavailbility and Mass Balance Recovery of the Product1
1CompletedBasic ScienceRenally Impaired Subjects1
1CompletedTreatmentBuprenorphine Withdrawal Syndrome / Opioid Dependence1
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentHepatic Failure1
1CompletedTreatmentHeroin Dependence1
1CompletedTreatmentMethadone Withdrawal Syndrome / Opioid Dependence2
1CompletedTreatmentOpioid-Related Disorders1
1CompletedTreatmentOpioid-Related Disorders / Substance-Related Disorders2
1TerminatedTreatmentCocaine Related Disorders1
2CompletedBasic ScienceMarijuana Dependence1
2CompletedTreatmentOpioid-Related Disorders1
2, 3CompletedTreatmentCannabis Dependence / Marijuana Dependence1
3CompletedTreatmentAcute Opioid Withdrawal Syndrome / Opioid Dependence1
3CompletedTreatmentOpiate Addiction1
3CompletedTreatmentOpiate withdrawal symptoms1
3CompletedTreatmentOpioid-Related Disorders1
4CompletedTreatmentOpiate Dependent Patients Who Are Undergoing Inpatient Detoxification in Singapore1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)221-223U.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 RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0bta-5090000000-966c69c881b261c7d39d

Taxonomy

Description
This compound belongs to the class of organic compounds known as dichlorobenzenes. These are compounds containing a benzene with exactly two chlorine atoms attached to it.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Halobenzenes
Direct Parent
Dichlorobenzenes
Alternative Parents
Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Imidolactams / Aryl chlorides / Imidazolines / Propargyl-type 1,3-dipolar organic compounds / Carboximidamides / Carboxamidines / Azacyclic compounds
show 3 more
Substituents
Phenoxy compound / 1,3-dichlorobenzene / Phenol ether / Alkyl aryl ether / Aryl chloride / Aryl halide / Imidolactam / 2-imidazoline / Amidine / Carboxylic acid amidine
show 15 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
aromatic ether, imidazoles, carboxamidine, dichlorobenzene (CHEBI:51368)

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 oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
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]

Drug created on October 21, 2007 16:23 / Updated on December 01, 2017 17:17