Identification
NameDroxidopa
Accession NumberDB06262
TypeSmall Molecule
GroupsApproved, Investigational
Description

Droxidopa is a precursor of noradrenaline that is used in the treatment of Parkinsonism. It is approved for use in Japan and is currently in trials in the U.S. The racaemic form (dl-threo-3,4-dihydroxyphenylserine) has also been used, and has been investigated in the treatment of orthostatic hypotension. There is a deficit of noradrenaline as well as of dopamine in Parkinson's disease and it has been proposed that this underlies the sudden transient freezing seen usually in advanced disease.

Though L-DOPS has been used in Japan and Southeast Asia already for some time, it is also currently in clinical trials at the phase III point in the United States (U.S.), Canada, Australia, and throughout Europe. Provided L-DOPS successfully completes clinical trials, it could be approved for the treatment of neurogenic orthostatic hypotension (NOH) as early as 2011. Additionally, phase II clinical trials for intradialytic hypotension are also underway. Chelsea Therapeutics obtained orphan drug status (ODS) for L-DOPS in the U.S. for NOH, and that of which associated with Parkinson's disease , pure autonomic failure, and multiple system atrophy, and is the pharmaceutical company developing it in that country.

Structure
Thumb
Synonyms
DOPS
L-Dihydroxyphenylserine
L-DOPS
L-threo-dihydroxyphenylserine
External IDs SM 5688 / SM-5688
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NortheraCapsule100 mg/1OralLundbeck Pharmaceuticals Llc2014-09-01Not applicableUs
NortheraCapsule200 mg/1OralLundbeck Pharmaceuticals Llc2014-09-01Not applicableUs
NortheraCapsule300 mg/1OralLundbeck Pharmaceuticals Llc2014-09-01Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
DopsNot Available
Brand mixturesNot Available
Categories
UNIIJ7A92W69L7
CAS number23651-95-8
WeightAverage: 213.189
Monoisotopic: 213.063722458
Chemical FormulaC9H11NO5
InChI KeyQXWYKJLNLSIPIN-JGVFFNPUSA-N
InChI
InChI=1S/C9H11NO5/c10-7(9(14)15)8(13)4-1-2-5(11)6(12)3-4/h1-3,7-8,11-13H,10H2,(H,14,15)/t7-,8+/m0/s1
IUPAC Name
(2S,3R)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid
SMILES
N[C@@H]([C@H](O)C1=CC(O)=C(O)C=C1)C(O)=O
Pharmacology
Indication

For treatment of neurogenic orthostatic hypotension (NOH) associated with various disorders including Multiple System Atrophy, Familial Amyloid Polyneuropathy, hemodialysis induced hypotension and Parkinson's Disease. Also investigated for use/treatment in neurologic disorders, nephropathy, blood (blood forming organ disorders, unspecified), and dizzy/fainting spells.

Structured Indications
Pharmacodynamics

Droxidopa is an orally active synthetic precursor of norepinephrine that increases the deficient supply of norepinephrine in patients with NOH, thereby improving orthostatic blood pressure and alleviating associated symptoms of lightheadedness, dizziness, blurred vision, and syncope through the induction of tachycardia (increased heart rate) and hypertension.

Mechanism of action

Droxidopa crosses the blood-brain barrier where it is converted to norepinephrine via decarboxylation by L-aromatic-amino-acid decarboxylase. Increased levels of norepinephrine in the central nervous system (CNS) may be beneficial to patients in a wide range of indications. Norephinephrine acts at alpha-adrenergic receptors as a vasoconstrictor and at beta-adrenergic receptors as a heart stimulator and artery dilator.

TargetKindPharmacological actionActionsOrganismUniProt ID
Alpha-1A adrenergic receptorProteinyes
agonist
HumanP35348 details
Alpha-1B adrenergic receptorProteinyes
agonist
HumanP35368 details
Alpha-1D adrenergic receptorProteinyes
agonist
HumanP25100 details
Alpha-2A adrenergic receptorProteinyes
agonist
HumanP08913 details
Alpha-2B adrenergic receptorProteinyes
agonist
HumanP18089 details
Alpha-2C adrenergic receptorProteinyes
agonist
HumanP18825 details
Beta-1 adrenergic receptorProteinyes
agonist
HumanP08588 details
Beta-2 adrenergic receptorProteinyes
agonist
HumanP07550 details
Beta-3 adrenergic receptorProteinyes
agonist
HumanP13945 details
Phenylalanine-4-hydroxylaseProteinno
inhibitor
HumanP00439 details
Related Articles
Absorption

Oral bioavailability is 90%.

Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Droxidopa is metabolized by aromatic L-amino acid decarboxylase.

Route of elimination

Droxidopa is mainly excreted in the urine, with the main metabolite being 3-O-methyldihydroxyphenylserine.

Half life

2-3 hours.

ClearanceNot Available
Toxicity

Droxidopa has minimal toxic effects and an acute, oral LD50 of more than 5 g/kg in mice, rats, dogs, and monkeys. Side effects occur in in 0.78% of patients and include nausea, headache, increased blood pressure, hallucination, and anorexia.

Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when 7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE is combined with Droxidopa.Experimental
AcebutololDroxidopa may increase the atrioventricular blocking (AV block) activities of Acebutolol.Approved
AlfuzosinAlfuzosin may decrease the vasoconstricting activities of Droxidopa.Approved, Investigational
AlmotriptanAlmotriptan may increase the hypertensive activities of Droxidopa.Approved, Investigational
AlprenololAlprenolol may decrease the bronchodilatory activities of Droxidopa.Approved, Withdrawn
AmineptineAmineptine may decrease the antihypertensive activities of Droxidopa.Illicit, Withdrawn
AmitriptylineAmitriptyline may decrease the antihypertensive activities of Droxidopa.Approved
ApomorphineApomorphine may increase the hypertensive activities of Droxidopa.Approved, Investigational
ArotinololDroxidopa may increase the atrioventricular blocking (AV block) activities of Arotinolol.Approved
AtenololDroxidopa may increase the atrioventricular blocking (AV block) activities of Atenolol.Approved
AtomoxetineAtomoxetine may increase the tachycardic activities of Droxidopa.Approved
BefunololDroxidopa may increase the atrioventricular blocking (AV block) activities of Befunolol.Experimental
BendroflumethiazideDroxidopa may increase the hypokalemic activities of Bendroflumethiazide.Approved
BenmoxinThe risk or severity of adverse effects can be increased when Benmoxin is combined with Droxidopa.Withdrawn
Benzylpenicilloyl PolylysineDroxidopa may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BetahistineThe therapeutic efficacy of Droxidopa can be decreased when used in combination with Betahistine.Approved
BetaxololDroxidopa may increase the atrioventricular blocking (AV block) activities of Betaxolol.Approved
BevantololDroxidopa may increase the atrioventricular blocking (AV block) activities of Bevantolol.Approved
BisoprololDroxidopa may increase the atrioventricular blocking (AV block) activities of Bisoprolol.Approved
BopindololBopindolol may decrease the bronchodilatory activities of Droxidopa.Approved
BromocriptineBromocriptine may increase the hypertensive activities of Droxidopa.Approved, Investigational
BucindololDroxidopa may increase the atrioventricular blocking (AV block) activities of Bucindolol.Investigational
BufuralolDroxidopa may increase the atrioventricular blocking (AV block) activities of Bufuralol.Experimental, Investigational
BumetanideDroxidopa may increase the hypokalemic activities of Bumetanide.Approved
BupranololBupranolol may decrease the bronchodilatory activities of Droxidopa.Approved
CabergolineCabergoline may increase the hypertensive activities of Droxidopa.Approved
CarbidopaThe therapeutic efficacy of Droxidopa can be decreased when used in combination with Carbidopa.Approved
CaroxazoneThe risk or severity of adverse effects can be increased when Caroxazone is combined with Droxidopa.Withdrawn
CarteololCarteolol may decrease the bronchodilatory activities of Droxidopa.Approved
CarvedilolDroxidopa may increase the atrioventricular blocking (AV block) activities of Carvedilol.Approved, Investigational
CeliprololDroxidopa may increase the atrioventricular blocking (AV block) activities of Celiprolol.Approved, Investigational
ChlorothiazideDroxidopa may increase the hypokalemic activities of Chlorothiazide.Approved, Vet Approved
ChlorthalidoneDroxidopa may increase the hypokalemic activities of Chlorthalidone.Approved
ClomipramineClomipramine may decrease the antihypertensive activities of Droxidopa.Approved, Vet Approved
CyclobenzaprineCyclobenzaprine may decrease the antihypertensive activities of Droxidopa.Approved
DesipramineDesipramine may decrease the antihypertensive activities of Droxidopa.Approved
DesvenlafaxineDesvenlafaxine may increase the tachycardic activities of Droxidopa.Approved
DihydroergotamineDihydroergotamine may increase the hypertensive activities of Droxidopa.Approved
DosulepinDosulepin may decrease the antihypertensive activities of Droxidopa.Approved
DoxazosinDoxazosin may decrease the vasoconstricting activities of Droxidopa.Approved
DoxepinDoxepin may decrease the antihypertensive activities of Droxidopa.Approved
DuloxetineDuloxetine may increase the tachycardic activities of Droxidopa.Approved
EletriptanEletriptan may increase the hypertensive activities of Droxidopa.Approved, Investigational
EphedraEphedra may increase the hypertensive activities of Droxidopa.Approved, Nutraceutical, Withdrawn
EphedrineEphedrine may increase the hypertensive activities of Droxidopa.Approved
Ergoloid mesylateErgoloid mesylate may increase the hypertensive activities of Droxidopa.Approved
ErgonovineErgonovine may increase the hypertensive activities of Droxidopa.Approved
ErgotamineErgotamine may increase the hypertensive activities of Droxidopa.Approved
EsmirtazapineEsmirtazapine may decrease the antihypertensive activities of Droxidopa.Investigational
EsmololDroxidopa may increase the atrioventricular blocking (AV block) activities of Esmolol.Approved
Etacrynic acidDroxidopa may increase the hypokalemic activities of Etacrynic acid.Approved
FrovatriptanFrovatriptan may increase the hypertensive activities of Droxidopa.Approved, Investigational
FurazolidoneThe risk or severity of adverse effects can be increased when Furazolidone is combined with Droxidopa.Approved, Vet Approved
FurosemideDroxidopa may increase the hypokalemic activities of Furosemide.Approved, Vet Approved
HydracarbazineThe risk or severity of adverse effects can be increased when Hydracarbazine is combined with Droxidopa.Experimental
HydrochlorothiazideDroxidopa may increase the hypokalemic activities of Hydrochlorothiazide.Approved, Vet Approved
HydroflumethiazideDroxidopa may increase the hypokalemic activities of Hydroflumethiazide.Approved
ImipramineImipramine may decrease the antihypertensive activities of Droxidopa.Approved
IndapamideDroxidopa may increase the hypokalemic activities of Indapamide.Approved
IndenololDroxidopa may increase the atrioventricular blocking (AV block) activities of Indenolol.Withdrawn
IndoraminIndoramin may decrease the vasoconstricting activities of Droxidopa.Withdrawn
IobenguaneThe therapeutic efficacy of Iobenguane can be decreased when used in combination with Droxidopa.Approved
IproclozideThe risk or severity of adverse effects can be increased when Iproclozide is combined with Droxidopa.Withdrawn
IproniazidThe risk or severity of adverse effects can be increased when Iproniazid is combined with Droxidopa.Withdrawn
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Droxidopa.Approved
LabetalolDroxidopa may increase the atrioventricular blocking (AV block) activities of Labetalol.Approved
LandiololDroxidopa may increase the atrioventricular blocking (AV block) activities of Aop200704.Investigational
LevomilnacipranLevomilnacipran may increase the tachycardic activities of Droxidopa.Approved
LisurideLisuride may increase the hypertensive activities of Droxidopa.Approved
MebanazineThe risk or severity of adverse effects can be increased when Mebanazine is combined with Droxidopa.Withdrawn
MethyclothiazideDroxidopa may increase the hypokalemic activities of Methyclothiazide.Approved
Methylene blueThe risk or severity of adverse effects can be increased when Methylene blue is combined with Droxidopa.Investigational
MetolazoneDroxidopa may increase the hypokalemic activities of Metolazone.Approved
MetoprololDroxidopa may increase the atrioventricular blocking (AV block) activities of Metoprolol.Approved, Investigational
MianserinThe therapeutic efficacy of Droxidopa can be decreased when used in combination with Mianserin.Approved
MidodrineMidodrine may increase the hypertensive activities of Droxidopa.Approved
MilnacipranMilnacipran may increase the tachycardic activities of Droxidopa.Approved
MinaprineThe risk or severity of adverse effects can be increased when Minaprine is combined with Droxidopa.Approved
MirtazapineMirtazapine may decrease the antihypertensive activities of Droxidopa.Approved
MoclobemideThe risk or severity of adverse effects can be increased when Moclobemide is combined with Droxidopa.Approved
NadololNadolol may decrease the bronchodilatory activities of Droxidopa.Approved
NaratriptanNaratriptan may increase the hypertensive activities of Droxidopa.Approved, Investigational
NebivololNebivolol may decrease the bronchodilatory activities of Droxidopa.Approved, Investigational
NialamideThe risk or severity of adverse effects can be increased when Nialamide is combined with Droxidopa.Withdrawn
NorepinephrineNorepinephrine may increase the hypertensive activities of Droxidopa.Approved
NortriptylineNortriptyline may decrease the antihypertensive activities of Droxidopa.Approved
OctamoxinThe risk or severity of adverse effects can be increased when Octamoxin is combined with Droxidopa.Withdrawn
OpipramolOpipramol may decrease the antihypertensive activities of Droxidopa.Investigational
OxprenololOxprenolol may decrease the bronchodilatory activities of Droxidopa.Approved
PargylineThe risk or severity of adverse effects can be increased when Pargyline is combined with Droxidopa.Approved
PenbutololPenbutolol may decrease the bronchodilatory activities of Droxidopa.Approved, Investigational
PergolidePergolide may increase the hypertensive activities of Droxidopa.Approved, Vet Approved, Withdrawn
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Droxidopa.Approved
PheniprazineThe risk or severity of adverse effects can be increased when Pheniprazine is combined with Droxidopa.Withdrawn
PhenoxypropazineThe risk or severity of adverse effects can be increased when Phenoxypropazine is combined with Droxidopa.Withdrawn
PindololPindolol may decrease the bronchodilatory activities of Droxidopa.Approved
PiretanideDroxidopa may increase the hypokalemic activities of Piretanide.Experimental
PirlindoleThe risk or severity of adverse effects can be increased when Pirlindole is combined with Droxidopa.Approved
PivhydrazineThe risk or severity of adverse effects can be increased when Pivhydrazine is combined with Droxidopa.Withdrawn
PolythiazideDroxidopa may increase the hypokalemic activities of Polythiazide.Approved
PractololDroxidopa may increase the atrioventricular blocking (AV block) activities of Practolol.Approved
PrazosinPrazosin may decrease the vasoconstricting activities of Droxidopa.Approved
PropranololPropranolol may decrease the bronchodilatory activities of Droxidopa.Approved, Investigational
ProtriptylineProtriptyline may decrease the antihypertensive activities of Droxidopa.Approved
QuinethazoneDroxidopa may increase the hypokalemic activities of Quinethazone.Approved
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Droxidopa.Approved
RizatriptanRizatriptan may increase the hypertensive activities of Droxidopa.Approved
RopiniroleRopinirole may increase the hypertensive activities of Droxidopa.Approved, Investigational
SafrazineThe risk or severity of adverse effects can be increased when Safrazine is combined with Droxidopa.Withdrawn
SelegilineThe risk or severity of adverse effects can be increased when Selegiline is combined with Droxidopa.Approved, Investigational, Vet Approved
SilodosinSilodosin may decrease the vasoconstricting activities of Droxidopa.Approved
SotalolSotalol may decrease the bronchodilatory activities of Droxidopa.Approved
SpironolactoneSpironolactone may decrease the vasoconstricting activities of Droxidopa.Approved
SumatriptanSumatriptan may increase the hypertensive activities of Droxidopa.Approved, Investigational
TamsulosinTamsulosin may decrease the vasoconstricting activities of Droxidopa.Approved, Investigational
TerazosinTerazosin may decrease the vasoconstricting activities of Droxidopa.Approved
TianeptineTianeptine may decrease the antihypertensive activities of Droxidopa.Approved
TimololTimolol may decrease the bronchodilatory activities of Droxidopa.Approved
ToloxatoneThe risk or severity of adverse effects can be increased when Toloxatone is combined with Droxidopa.Approved
TorasemideDroxidopa may increase the hypokalemic activities of Torasemide.Approved
Trans-2-PhenylcyclopropylamineThe risk or severity of adverse effects can be increased when Trans-2-Phenylcyclopropylamine is combined with Droxidopa.Experimental
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Droxidopa.Approved
TrichlormethiazideDroxidopa may increase the hypokalemic activities of Trichlormethiazide.Approved, Vet Approved
TrimazosinTrimazosin may decrease the vasoconstricting activities of Droxidopa.Experimental
TrimipramineTrimipramine may decrease the antihypertensive activities of Droxidopa.Approved
VenlafaxineVenlafaxine may increase the tachycardic activities of Droxidopa.Approved
VilazodoneVilazodone may increase the hypertensive activities of Droxidopa.Approved
VortioxetineVortioxetine may increase the hypertensive activities of Droxidopa.Approved
ZolmitriptanZolmitriptan may increase the hypertensive activities of Droxidopa.Approved, Investigational
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Kaufmann H: L-dihydroxyphenylserine (Droxidopa): a new therapy for neurogenic orthostatic hypotension: the US experience. Clin Auton Res. 2008 Mar;18 Suppl 1:19-24. doi: 10.1007/s10286-007-1002-2. Epub 2008 Mar 27. [PubMed:18368303 ]
  2. Balk SH, Yoshioka H, Yukawa H, Harayama S: Synthesis of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) with thermostabilized low-specific L-threonine aldolase from Streptomyces coelicolor A3(2). J Microbiol Biotechnol. 2007 May;17(5):721-7. [PubMed:18051291 ]
  3. Mathias CJ: L-dihydroxyphenylserine (Droxidopa) in the treatment of orthostatic hypotension: the European experience. Clin Auton Res. 2008 Mar;18 Suppl 1:25-9. doi: 10.1007/s10286-007-1005-z. Epub 2008 Mar 27. [PubMed:18368304 ]
  4. Goldstein DS: L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug. Cardiovasc Drug Rev. 2006 Fall-Winter;24(3-4):189-203. [PubMed:17214596 ]
  5. Goldstein DS, Holmes C, Kaufmann H, Freeman R: Clinical pharmacokinetics of the norepinephrine precursor L-threo-DOPS in primary chronic autonomic failure. Clin Auton Res. 2004 Dec;14(6):363-8. [PubMed:15666063 ]
External Links
ATC CodesC01CA27 — Droxidopa
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentArterial Hypotension / Spinal Cord Injuries (SCI)1
1CompletedTreatmentQTc Interval1
1CompletedTreatmentSymptomatic Neurogenic Orthostatic Hypotension1
1RecruitingBasic ScienceAutonomic Failure / Idiopathic orthostatic hypotension / Multiple System Atrophy (MSA) / Parkinson's Disease (PD) / Progressive autonomic failure1
1WithdrawnTreatmentEnd Stage Renal Disease (ESRD) / Renal Diseases1
1, 2TerminatedTreatmentAutonomic Nervous System Diseases / Multiple System Atrophy (MSA) / Parkinson's Disease (PD)1
1, 2TerminatedTreatmentOrthostatic Intolerance / Postural Orthostatic Tachycardia Syndrome (POTS)1
1, 2WithdrawnTreatmentGait Disorders, Neurologic1
2CompletedTreatmentAttention Deficit Hyperactivity Disorder (ADHD)1
2CompletedTreatmentFibromyalgia1
2CompletedTreatmentIntradialytic Hypotension1
2Enrolling by InvitationTreatmentCognitive Ability, General / Freezing of Gait / Parkinson's Disease (PD)1
2RecruitingTreatmentParkinson's Disease (PD)1
2RecruitingTreatmentPostural Tachycardia Syndrome (POTS) / Syncope / Vasovagal Syncope (VVS)1
2RecruitingTreatmentIdiopathic orthostatic hypotension1
2TerminatedTreatmentIdiopathic orthostatic hypotension / Myalgic Encephalomyelitis (ME) / Neurally Mediated Hypotension / Neurogenic Orthostatic Hypotension1
2WithdrawnTreatmentHSAN Type IV1
3CompletedTreatmentDopamine Beta Hydroxylase Deficiency / Multiple System Atrophy (MSA) / Neurogenic Orthostatic Hypotension / Non-Diabetic Autonomic Neuropathy1
3CompletedTreatmentDopamine Beta Hydroxylase Deficiency / Neurogenic Orthostatic Hypotension / Non-Diabetic Neuropathy / Primary Autonomic Failure1
3CompletedTreatmentDopamine Beta Hydroxylase Deficiency / Non-Diabetic Neuropathy / Primary Autonomic Failure / Symptomatic Neurogenic Orthostatic Hypotension (NOH)2
3CompletedTreatmentIdiopathic orthostatic hypotension / Parkinson's Disease (PD)1
3Enrolling by InvitationTreatmentAutonomic Nervous System Diseases / Dopamine Beta-Hydroxylase Deficiency / Idiopathic orthostatic hypotension / Orthostatic Intolerance1
3TerminatedTreatmentDopamine Beta Hydroxylase Deficiency / Multiple Systems Atrophy / Parkinson's Disease (PD) / Progressive autonomic failure / Symptomatic Neurogenic Orthostatic Hypotension1
3TerminatedTreatmentIdiopathic orthostatic hypotension1
4RecruitingTreatmentParkinson's Disease (PD)1
4RecruitingTreatmentParkinson's Disease (PD) / Parkinsonism / Tiredness1
4RecruitingTreatmentSymptomatic Neurogenic Orthostatic Hypotension1
Not AvailableApproved for MarketingNot AvailableDopamine Beta Hydroxylase (DBH) Deficiency1
Not AvailableCompletedTreatmentIdiopathic orthostatic hypotension / Shy-Drager Syndrome1
Not AvailableRecruitingTreatmentParkinson's Disease (PD)1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
CapsuleOral100 mg/1
CapsuleOral200 mg/1
CapsuleOral300 mg/1
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility15.3 mg/mLALOGPS
logP-2.4ALOGPS
logP-2.7ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)1.46ChemAxon
pKa (Strongest Basic)8.72ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area124.01 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity50.29 m3·mol-1ChemAxon
Polarizability19.85 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8412
Blood Brain Barrier-0.9305
Caco-2 permeable-0.8613
P-glycoprotein substrateNon-substrate0.7167
P-glycoprotein inhibitor INon-inhibitor0.9874
P-glycoprotein inhibitor IINon-inhibitor0.993
Renal organic cation transporterNon-inhibitor0.949
CYP450 2C9 substrateNon-substrate0.8401
CYP450 2D6 substrateNon-substrate0.8805
CYP450 3A4 substrateNon-substrate0.7587
CYP450 1A2 substrateNon-inhibitor0.8012
CYP450 2C9 inhibitorNon-inhibitor0.9573
CYP450 2D6 inhibitorNon-inhibitor0.9472
CYP450 2C19 inhibitorNon-inhibitor0.8565
CYP450 3A4 inhibitorNon-inhibitor0.76
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9562
Ames testNon AMES toxic0.7494
CarcinogenicityNon-carcinogens0.9262
BiodegradationReady biodegradable0.765
Rat acute toxicity1.3600 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9904
hERG inhibition (predictor II)Non-inhibitor0.9693
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as tyrosine and derivatives. These are compounds containing tyrosine or a derivative thereof resulting from reaction of tyrosine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentTyrosine and derivatives
Alternative ParentsPhenylalanine and derivatives / Phenylpropanoic acids / L-alpha-amino acids / Catechols / 1-hydroxy-2-unsubstituted benzenoids / 1-hydroxy-4-unsubstituted benzenoids / Aralkylamines / Beta hydroxy acids and derivatives / Benzene and substituted derivatives / Secondary alcohols
SubstituentsTyrosine or derivatives / Phenylalanine or derivatives / 3-phenylpropanoic-acid / Alpha-amino acid / L-alpha-amino acid / Catechol / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Beta-hydroxy acid / Aralkylamine
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsL-tyrosine derivative, catechol (CHEBI:31524 )

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
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) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
Uniprot Name:
Alpha-1A adrenergic receptor
Molecular Weight:
51486.005 Da
References
  1. Senard JM, Brefel-Courbon C, Rascol O, Montastruc JL: Orthostatic hypotension in patients with Parkinson's disease: pathophysiology and management. Drugs Aging. 2001;18(7):495-505. [PubMed:11482743 ]
  2. Bishop MJ: Recent advances in the discovery of alpha1-adrenoceptor agonists. Curr Top Med Chem. 2007;7(2):135-45. [PubMed:17266602 ]
  3. Du L, Li M: Modeling the interactions between alpha(1)-adrenergic receptors and their antagonists. Curr Comput Aided Drug Des. 2010 Sep;6(3):165-78. [PubMed:20412040 ]
  4. Lachnit WG, Tran AM, Clarke DE, Ford AP: Pharmacological characterization of an alpha 1A-adrenoceptor mediating contractile responses to noradrenaline in isolated caudal artery of rat. Br J Pharmacol. 1997 Mar;120(5):819-26. [PubMed:9138687 ]
  5. Burt RP, Chapple CR, Marshall I: The role of diacylglycerol and activation of protein kinase C in alpha 1A-adrenoceptor-mediated contraction to noradrenaline of rat isolated epididymal vas deferens. Br J Pharmacol. 1996 Jan;117(1):224-30. [PubMed:8825367 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
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) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1B
Uniprot ID:
P35368
Uniprot Name:
Alpha-1B adrenergic receptor
Molecular Weight:
56835.375 Da
References
  1. Bishop MJ: Recent advances in the discovery of alpha1-adrenoceptor agonists. Curr Top Med Chem. 2007;7(2):135-45. [PubMed:17266602 ]
  2. Du L, Li M: Modeling the interactions between alpha(1)-adrenergic receptors and their antagonists. Curr Comput Aided Drug Des. 2010 Sep;6(3):165-78. [PubMed:20412040 ]
  3. Testa R, Guarneri L, Poggesi E, Simonazzi I, Taddei C, Leonardi A: Mediation of noradrenaline-induced contractions of rat aorta by the alpha 1B-adrenoceptor subtype. Br J Pharmacol. 1995 Feb;114(4):745-50. [PubMed:7773533 ]
  4. Izzo NJ Jr, Colucci WS: Regulation of alpha 1B-adrenergic receptor half-life: protein synthesis dependence and effect of norepinephrine. Am J Physiol. 1994 Mar;266(3 Pt 1):C771-5. [PubMed:8166240 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Alpha1-adrenergic receptor activity
Specific Function:
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name:
ADRA1D
Uniprot ID:
P25100
Uniprot Name:
Alpha-1D adrenergic receptor
Molecular Weight:
60462.205 Da
References
  1. Bishop MJ: Recent advances in the discovery of alpha1-adrenoceptor agonists. Curr Top Med Chem. 2007;7(2):135-45. [PubMed:17266602 ]
  2. Du L, Li M: Modeling the interactions between alpha(1)-adrenergic receptors and their antagonists. Curr Comput Aided Drug Des. 2010 Sep;6(3):165-78. [PubMed:20412040 ]
  3. Kenny BA, Chalmers DH, Philpott PC, Naylor AM: Characterization of an alpha 1D-adrenoceptor mediating the contractile response of rat aorta to noradrenaline. Br J Pharmacol. 1995 Jul;115(6):981-6. [PubMed:7582530 ]
  4. Testa R, Destefani C, Guarneri L, Poggesi E, Simonazzi I, Taddei C, Leonardi A: The alpha 1d-adrenoceptor subtype is involved in the noradrenaline-induced contractions of rat aorta. Life Sci. 1995;57(13):PL159-63. [PubMed:7674815 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Thioesterase binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianser...
Gene Name:
ADRA2A
Uniprot ID:
P08913
Uniprot Name:
Alpha-2A adrenergic receptor
Molecular Weight:
48956.275 Da
References
  1. Davis MP: Recent advances in the treatment of pain. F1000 Med Rep. 2010 Aug 19;2:63. doi: 10.3410/M2-63. [PubMed:21173850 ]
  2. Giovannoni MP, Ghelardini C, Vergelli C, Dal Piaz V: Alpha2-agonists as analgesic agents. Med Res Rev. 2009 Mar;29(2):339-68. doi: 10.1002/med.20134. [PubMed:18680204 ]
  3. Nyronen T, Pihlavisto M, Peltonen JM, Hoffren AM, Varis M, Salminen T, Wurster S, Marjamaki A, Kanerva L, Katainen E, Laaksonen L, Savola JM, Scheinin M, Johnson MS: Molecular mechanism for agonist-promoted alpha(2A)-adrenoceptor activation by norepinephrine and epinephrine. Mol Pharmacol. 2001 May;59(5):1343-54. [PubMed:11306720 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Epinephrine 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 clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phent...
Gene Name:
ADRA2B
Uniprot ID:
P18089
Uniprot Name:
Alpha-2B adrenergic receptor
Molecular Weight:
49565.8 Da
References
  1. Davis MP: Recent advances in the treatment of pain. F1000 Med Rep. 2010 Aug 19;2:63. doi: 10.3410/M2-63. [PubMed:21173850 ]
  2. Giovannoni MP, Ghelardini C, Vergelli C, Dal Piaz V: Alpha2-agonists as analgesic agents. Med Res Rev. 2009 Mar;29(2):339-68. doi: 10.1002/med.20134. [PubMed:18680204 ]
  3. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. [PubMed:18064417 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Protein homodimerization activity
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name:
ADRA2C
Uniprot ID:
P18825
Uniprot Name:
Alpha-2C adrenergic receptor
Molecular Weight:
49521.585 Da
References
  1. Davis MP: Recent advances in the treatment of pain. F1000 Med Rep. 2010 Aug 19;2:63. doi: 10.3410/M2-63. [PubMed:21173850 ]
  2. Giovannoni MP, Ghelardini C, Vergelli C, Dal Piaz V: Alpha2-agonists as analgesic agents. Med Res Rev. 2009 Mar;29(2):339-68. doi: 10.1002/med.20134. [PubMed:18680204 ]
  3. Rump LC, Bohmann C, Schaible U, Schollhorn J, Limberger N: Alpha 2C-adrenoceptor-modulated release of noradrenaline in human right atrium. Br J Pharmacol. 1995 Nov;116(6):2617-24. [PubMed:8590979 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Receptor signaling protein activity
Specific Function:
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling.
Gene Name:
ADRB1
Uniprot ID:
P08588
Uniprot Name:
Beta-1 adrenergic receptor
Molecular Weight:
51322.1 Da
References
  1. Mersmann HJ: Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action. J Anim Sci. 1998 Jan;76(1):160-72. [PubMed:9464897 ]
  2. El-Armouche A, Eschenhagen T: Beta-adrenergic stimulation and myocardial function in the failing heart. Heart Fail Rev. 2009 Dec;14(4):225-41. doi: 10.1007/s10741-008-9132-8. [PubMed:19110970 ]
  3. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. [PubMed:18064417 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Protein homodimerization activity
Specific Function:
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.
Gene Name:
ADRB2
Uniprot ID:
P07550
Uniprot Name:
Beta-2 adrenergic receptor
Molecular Weight:
46458.32 Da
References
  1. Mersmann HJ: Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action. J Anim Sci. 1998 Jan;76(1):160-72. [PubMed:9464897 ]
  2. Sanders VM: The role of norepinephrine and beta-2-adrenergic receptor stimulation in the modulation of Th1, Th2, and B lymphocyte function. Adv Exp Med Biol. 1998;437:269-78. [PubMed:9666280 ]
  3. Tarizzo VI, Coppes RP, Dahlof C, Zaagsma J: Pre- and postganglionic stimulation-induced noradrenaline overflow is markedly facilitated by a prejunctional beta 2-adrenoceptor-mediated control mechanism in the pithed rat. Naunyn Schmiedebergs Arch Pharmacol. 1994 Jun;349(6):570-7. [PubMed:7969507 ]
  4. El-Armouche A, Eschenhagen T: Beta-adrenergic stimulation and myocardial function in the failing heart. Heart Fail Rev. 2009 Dec;14(4):225-41. doi: 10.1007/s10741-008-9132-8. [PubMed:19110970 ]
  5. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. [PubMed:18064417 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Protein homodimerization activity
Specific Function:
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.
Gene Name:
ADRB3
Uniprot ID:
P13945
Uniprot Name:
Beta-3 adrenergic receptor
Molecular Weight:
43518.615 Da
References
  1. Coman OA, Paunescu H, Ghita I, Coman L, Badararu A, Fulga I: Beta 3 adrenergic receptors: molecular, histological, functional and pharmacological approaches. Rom J Morphol Embryol. 2009;50(2):169-79. [PubMed:19434307 ]
  2. Mersmann HJ: Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action. J Anim Sci. 1998 Jan;76(1):160-72. [PubMed:9464897 ]
  3. El-Armouche A, Eschenhagen T: Beta-adrenergic stimulation and myocardial function in the failing heart. Heart Fail Rev. 2009 Dec;14(4):225-41. doi: 10.1007/s10741-008-9132-8. [PubMed:19110970 ]
  4. Gilsbach R, Hein L: Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline. Handb Exp Pharmacol. 2008;(184):261-88. [PubMed:18064417 ]
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
inhibitor
General Function:
Phenylalanine 4-monooxygenase activity
Specific Function:
Not Available
Gene Name:
PAH
Uniprot ID:
P00439
Uniprot Name:
Phenylalanine-4-hydroxylase
Molecular Weight:
51861.565 Da
References
  1. Martinez A, Andersson KK, Haavik J, Flatmark T: EPR and 1H-NMR spectroscopic studies on the paramagnetic iron at the active site of phenylalanine hydroxylase and its interaction with substrates and inhibitors. Eur J Biochem. 1991 Jun 15;198(3):675-82. [PubMed:1646718 ]
  2. Martinez A, Haavik J, Flatmark T: Cooperative homotropic interaction of L-noradrenaline with the catalytic site of phenylalanine 4-monooxygenase. Eur J Biochem. 1990 Oct 5;193(1):211-9. [PubMed:2226440 ]
  3. Molinoff PB: The regulation of the noradrenergic neuron. J Psychiatr Res. 1974;11:339-45. [PubMed:4156788 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Pyridoxal phosphate binding
Specific Function:
Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
Gene Name:
DDC
Uniprot ID:
P20711
Uniprot Name:
Aromatic-L-amino-acid decarboxylase
Molecular Weight:
53925.815 Da
References
  1. Goldstein DS: L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug. Cardiovasc Drug Rev. 2006 Fall-Winter;24(3-4):189-203. [PubMed:17214596 ]
  2. Maruyama W, Naoi M, Narabayashi H: [The effect of droxidopa on the monoamine metabolsim in the human brain]. Rinsho Shinkeigaku. 1994 Oct;34(10):985-90. [PubMed:7834959 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Norepinephrine:sodium symporter activity
Specific Function:
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A2
Uniprot ID:
P23975
Uniprot Name:
Sodium-dependent noradrenaline transporter
Molecular Weight:
69331.42 Da
References
  1. Habecker BA, Willison BD, Shi X, Woodward WR: Chronic depolarization stimulates norepinephrine transporter expression via catecholamines. J Neurochem. 2006 May;97(4):1044-51. Epub 2006 Mar 29. [PubMed:16573647 ]
  2. Bonisch H, Bruss M: The norepinephrine transporter in physiology and disease. Handb Exp Pharmacol. 2006;(175):485-524. [PubMed:16722247 ]
  3. Mandela P, Ordway GA: KCl stimulation increases norepinephrine transporter function in PC12 cells. J Neurochem. 2006 Sep;98(5):1521-30. Epub 2006 Jul 31. [PubMed:16879714 ]
  4. Gutman DA, Owens MJ: Serotonin and norepinephrine transporter binding profile of SSRIs. Essent Psychopharmacol. 2006;7(1):35-41. [PubMed:16989291 ]
  5. Ksiazek P, Buraczynska K, Buraczynska M: Norepinephrine transporter gene (NET) polymorphism in patients with type 2 diabetes. Kidney Blood Press Res. 2006;29(6):338-43. Epub 2006 Nov 23. [PubMed:17124432 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Transporter activity
Specific Function:
Sodium-independent transporter that mediates the update of aromatic acid. Can function as a net efflux pathway for aromatic amino acids in the basosolateral epithelial cells (By similarity).
Gene Name:
SLC16A10
Uniprot ID:
Q8TF71
Uniprot Name:
Monocarboxylate transporter 10
Molecular Weight:
55492.07 Da
References
  1. Kim DK, Kanai Y, Chairoungdua A, Matsuo H, Cha SH, Endou H: Expression cloning of a Na+-independent aromatic amino acid transporter with structural similarity to H+/monocarboxylate transporters. J Biol Chem. 2001 May 18;276(20):17221-8. Epub 2001 Feb 20. [PubMed:11278508 ]
Drug created on March 19, 2008 10:20 / Updated on June 11, 2017 21:01