Identification

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

Lofexidine is a non-opioid centrally acting alpha2-adrenergic receptor agonist that was first approved for the treatment of opioid withdrawal in the United Kingdom in 1992.[2] It was first studied to be used as an antihypertensive in 1980 but its researched was stopped as it was less effective to treat hypertension than clonidine.[6] Lofexidine was then retaken for the treatment of opioid withdrawal as it was seen to be the more economic and with fewer side effects analog of clonidine.[5] Lofexidine was developed by US Woldmeds LLC and it got approved by the FDA on May 16, 2018.[8]

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

Lofexidine is indicated for mitigation of symptoms associated with acute withdrawal from opioids and for facilitation of the completion of opioid discontinuation treatment. It is the first non-opioid medication for the symptomatic management of opioid discontinuation.[9]

The opioid withdrawal syndrome is a debilitating manifestation of opioid dependence.[3] This condition is extremely unpleasant lasting several days with some of the main features being abdominal pain, nausea, diarrhea, mydriasis, lacrimation, and piloerection. These symptoms are often observed after abrupt reductions in the opioid dose and can be resolved by re-administration of the opioid.[4]

Structured Indications
Not Available
Pharmacodynamics

In clinical trials, lofexidine presented more severe opioid withdrawal effects than the ones observed with methadone. On the other hand, in clinical trials of methadone withdrawal, lofexidine effectively reduced withdrawal symptoms especially hypotension.[5] The clinical reports have also indicated that lofexidine presents a better outcome when used briefly.[6] In phase 3 clinical trials, lofexidine was shown to generate a significantly higher completion rate of opioid discontinuation. Some pharmacological studies were performed and there was no off-target effects reported.[9]

Mechanism of action

Lofexidine is a potent alpha2-adrenergic receptor agonist with some moderate agonistic affinity towards alpha1a-adrenoreceptor and 5-HT1a, 5-HT7, 5HT2c and 5HT1d receptors.[9]

The alpha2-adrenergic receptor is normally targeted by norepinephrine and its activation inhibit the synthesis of cAMP which in turn leads to potassium efflux and suppression of neural firing and inhibition of norepinephrine release. All this activity can reduce the heart rate, blood pressure and attenuate sympathetic stress response.[9]

Opioids inhibit cAMP in the noradrenergic neurons and its discontinuation produces a rise in the level of cAMP. This will generate an increase in norepinephrine which is associated with the symptoms of withdrawal. The magnitude of the effect is augmented by chronic opioid use due to the compensatory mechanisms of continuous negative feedback. Therefore, a chronic opioid use translated in an exacerbated production of cAMP and norepinephrine release.[9]

Lofexidine replaces the opioid-driven inhibition of cAMP production by activating the alpha2-adrenergic receptor and moderates the symptoms of opioid withdrawal. This effect is performed without interacting with opioid receptors which mediate other activities of opioid dependence or addiction.[9]

TargetActionsOrganism
AAlpha-2A adrenergic receptor
agonist
Human
NAlpha-1A adrenergic receptor
agonist
Human
N5-hydroxytryptamine receptor 1A
agonist
Human
N5-hydroxytryptamine receptor 7
agonist
Human
N5-hydroxytryptamine receptor 2C
agonist
Human
N5-hydroxytryptamine receptor 1D
agonist
Human
Absorption

Lofexidine has a good oral bioavailability and the peak plasma concentration occurs after 2-5 hours of oral administration.[6] The bioavailability is registered to be even higher than 72%.[7] About 30% of the administered dose of lofexidine is lost during first-pass metabolism. The absorption is registered to be very rapidly recirculated in the gut. After oral administration of 0.8 mg of lofexidine, a maximal dose of 1.26 ng/ml is achieved after 3 hours.[9]

Volume of distribution

Lofexidine has a volume of distribution of 300 L which indicated that it distributes readily into the tissues.[9]

Protein binding

The protein binding of lofexidine is determined to be moderate and it represents about 55% of the administered dose.[9]

Metabolism

Lofexidine metabolic ratio is highly variable among people.[6] It is metabolized mainly by the activity of CYP2D6 and in a minor degree by CYP1A2 and CYP2C19. These enzymes catalyze the hydroxylation of lofexidine and the opening of imidazoline ring to form N-(2-aminoethyl)-2-(2,6-dichlorophenoxy)propanamide. This metabolite is deamidated and forms 2-(2,6-dichlorophenoxy) propionic acid and 2,6-dichlorophenol. These three main metabolites are inactive.[9]

Route of elimination

The elimination of lofexidine is primarily done through the renal system and it represents 94% of the administered dose while in the elimination in feces corresponds to only 0.93%.[6] From the eliminated dose in urine, about 10% is formed by unchanged drug and 5% is constituted by the first hydrolysis product N-(2-aminoethyl)-2-(2,6-dichlorophenoxy)propanamide. 2,6-dichlorophenol represents the majority of the administered dose by occupying about 80% of the administered dose.[9]

Half life

The reported elimination half-life of lofexidine is 11 hours.[7]

Clearance

The total elimination clearance following intravenous administration os 17.6 L/h.[9]

Toxicity

Lofexidine did not exhibit genotoxic, mutagenic nor mutagenic potential. Administration at gestational period showed a reduction in the nenatal weight, survival and increased abortions.[9]

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, Investigational
AcemetacinThe therapeutic efficacy of Lofexidine can be decreased when used in combination with Acemetacin.Approved, Experimental, Investigational
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, Investigational
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.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, Investigational
BarbexacloneBarbexaclone may increase the hypotensive activities of Lofexidine.Experimental
BarbitalBarbital may increase the hypotensive activities of Lofexidine.Illicit
BarnidipineLofexidine may increase the antihypertensive activities of Barnidipine.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, Investigational
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
BromocriptineBromocriptine may increase the hypertensive and vasoconstricting 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 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 and vasoconstricting 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, Investigational
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, Investigational, 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, Investigational
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, Investigational, 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, Investigational
DesvenlafaxineDesvenlafaxine may increase the tachycardic activities of Lofexidine.Approved, Investigational
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, Investigational
DiethylnorspermineLofexidine may increase the hypotensive activities of Diethylnorspermine.Investigational
DihydralazineDihydralazine may increase the hypotensive activities of Lofexidine.Approved, Investigational
DihydroergotamineDihydroergotamine may increase the hypertensive and vasoconstricting activities of Lofexidine.Approved, Investigational
DiltiazemDiltiazem may increase the hypotensive activities of Lofexidine.Approved, Investigational
DinutuximabThe risk or severity of adverse effects can be increased when Lofexidine is combined with Dinutuximab.Approved, Investigational
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, Investigational
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 and vasoconstricting activities of Lofexidine.Approved
ErgonovineErgonovine may increase the hypertensive and vasoconstricting activities of Lofexidine.Approved
ErgotamineErgotamine may increase the hypertensive and vasoconstricting 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, Investigational
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
IloprostThe risk or severity of adverse effects can be increased when Iloprost is combined with 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, Investigational
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, Investigational
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, Investigational
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, Investigational
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 and vasoconstricting activities of Lofexidine.Approved
MethylnaltrexoneThe risk or severity of adverse effects can be increased when Lofexidine is combined with Methylnaltrexone.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, Investigational
MinaprineMinaprine may increase the hypotensive activities of Lofexidine.Approved
MinoxidilMinoxidil may increase the hypotensive activities of Lofexidine.Approved, Investigational
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, Investigational
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, Investigational
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, Investigational
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, Investigational
Nitrous acidThe risk or severity of adverse effects can be increased when Lofexidine is combined with Nitrous acid.Approved, Investigational
NortriptylineNortriptyline may decrease the antihypertensive activities of Lofexidine.Approved
ObinutuzumabLofexidine may increase the hypotensive activities of Obinutuzumab.Approved, Investigational
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, Investigational
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, Investigational, 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, Investigational
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.Approved
PindololLofexidine may increase the atrioventricular blocking (AV block) activities of Pindolol.Approved, Investigational
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, Investigational
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.Approved, 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
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
TerazosinTerazosin may decrease the vasoconstricting activities of Lofexidine.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, Investigational
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
TranylcypromineTranylcypromine may increase the hypotensive activities of Lofexidine.Approved, Investigational
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, Investigational
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, Investigational
YohimbineYohimbine may decrease the antihypertensive activities of Lofexidine.Approved, Investigational, 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]
  2. Haney M, Hart CL, Vosburg SK, Comer SD, Reed SC, Foltin RW: Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse. Psychopharmacology (Berl). 2008 Mar;197(1):157-68. doi: 10.1007/s00213-007-1020-8. Epub 2007 Dec 27. [PubMed:18161012]
  3. Rehni AK, Jaggi AS, Singh N: Opioid withdrawal syndrome: emerging concepts and novel therapeutic targets. CNS Neurol Disord Drug Targets. 2013 Feb 1;12(1):112-25. [PubMed:23244430]
  4. Juurlink DN, Dhalla IA: Dependence and addiction during chronic opioid therapy. J Med Toxicol. 2012 Dec;8(4):393-9. doi: 10.1007/s13181-012-0269-4. [PubMed:23073725]
  5. Ries R. and Miller S. (2009). Principles of Addiction Medicine (4th ed.). Lippincott Williams & Wilkins. [ISBN:978-0-7817-7477-2]
  6. Strain E. and Stitzer M. (2006). The treatment of Opiod Dependence. The Johns Hopkins University Press. [ISBN:0-8018-8303-2]
  7. Zaragoza Dorwald F. (2012). Lead optimization for medicinal chemists. Wiley-VCH.
  8. FDA News [Link]
  9. FDA reports [Link]
External Links
Human Metabolome Database
HMDB0015606
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
FDA label
Download (530 KB)
MSDS
Download (72.7 KB)

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.
boiling point (°C)421.5 ºC at 760 mm Hg'MSDS'
water solubilitySoluble'MSDS'
logP5.37FDA Advisory Committee Briefing Document.
pKa9.43FDA Advisory Committee Briefing Document.
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]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Agonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. FDA reports [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Agonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
Molecular Weight
46106.335 Da
References
  1. FDA reports [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Agonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR7
Uniprot ID
P34969
Uniprot Name
5-hydroxytryptamine receptor 7
Molecular Weight
53554.43 Da
References
  1. FDA reports [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Agonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. FDA reports [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Agonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1D
Uniprot ID
P28221
Uniprot Name
5-hydroxytryptamine receptor 1D
Molecular Weight
41906.38 Da
References
  1. FDA reports [Link]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. FDA reports [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. FDA reports [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. FDA reports [Link]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Efflux transmembrane transporter activity
Specific Function
Drug efflux transporter present in a number of stem cells that acts as a regulator of cellular differentiation. Able to mediate efflux from cells of the rhodamine dye and of the therapeutic drug do...
Gene Name
ABCB5
Uniprot ID
Q2M3G0
Uniprot Name
ATP-binding cassette sub-family B member 5
Molecular Weight
138639.48 Da
References
  1. FDA reports [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. FDA reports [Link]

Drug created on October 21, 2007 16:23 / Updated on May 18, 2018 14:26