Droxidopa

Summary

Droxidopa (CHEMBL2103827) is an approved small-molecule prodrug (ATC C01CA27) targeting CHRM1; indicated across 8 conditions including orthostatic hypotension and cardiovascular disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C01CA27
• Targets: 1 (CHRM1)
• Indications: 8 conditions
• Clinical trials: 39
• Chemistry: 213.19 Da · C9H11NO5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2103827
Name	Droxidopa
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	92974
ChEBI	CHEBI:31524
ATC	C01CA27
Molecular formula	C9H11NO5
Molecular weight	213.19
InChIKey	QXWYKJLNLSIPIN-JGVFFNPUSA-N

SMILES: C1=CC(=C(C=C1[C@H]([C@@H](C(=O)O)N)O)O)O

IUPAC name: (2S,3R)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid

ChEBI definition: A serine derivative that is L-serine substituted at the β-position by a 3,4-dihydroxyphenyl group. A prodrug for noradrenalone, it is used for treatment of neurogenic orthostatic hypotension

Pharmacological roles (ChEBI): prodrug, vasoconstrictor agent, antihypertensive agent.

Also known as: DOPS, Droxidopa, L-DOPS, L-threo-dops, Northera, Droxydopa, DROXIDOPA, DROXIDOPA (L-DOPS), droxidopa, Droxidopa (L-DOPS)

Patent coverage: 119 distinct patent families (268 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 223 (83%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
CHRM1	M1 receptor	Antagonist	7.1	0.2%	P11229

Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: Nuclear receptor subfamily 1 group I member 2, Prostaglandin G/H synthase 1, Alpha-1A adrenergic receptor, Nuclear receptor subfamily 1 group I member 2.

Bioactivity

ChEMBL activities: 2 potent at pChembl ≥ 5 of 5 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
NR1I2	8.4	EC50	4	nM	CHEMBL_ACT_15463788
NR1I2	5.5	EC50	3200	nM	CHEMBL_ACT_15465480

Target pathways

Aggregated over 1 target gene(s): CHRM1.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	1	CHRM1
Signaling by GPCR	1	CHRM1
Class A/1 (Rhodopsin-like receptors)	1	CHRM1
Amine ligand-binding receptors	1	CHRM1
GPCR downstream signalling	1	CHRM1
Muscarinic acetylcholine receptors	1	CHRM1
G alpha (q) signalling events	1	CHRM1
GPCR ligand binding	1	CHRM1

Dominant GO biological processes

GO term	Targets
signal transduction	1
G protein-coupled receptor signaling pathway	1
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	1
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway	1
G protein-coupled acetylcholine receptor signaling pathway	1
chemical synaptic transmission	1
neuromuscular synaptic transmission	1
nervous system development	1
regulation of locomotion	1
positive regulation of monoatomic ion transport	1
saliva secretion	1
cognition	1
regulation of postsynaptic membrane potential	1

Indications & clinical

Indications

8 indications (3 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
orthostatic hypotension	4	MONDO:0005469	EFO:0005252
cardiovascular disorder	4	MONDO:0004995	EFO:0000319
multiple system atrophy	4	MONDO:0007803	EFO:1001050
hypotensive disorder	2	MONDO:0005468	EFO:0005251
fibromyalgia	2	MONDO:0005546	EFO:0005687
attention deficit-hyperactivity disorder	2	MONDO:0007743	EFO:0003888
Parkinson disease	2	MONDO:0005180	MONDO:0005180
postural orthostatic tachycardia syndrome	1	MONDO:0011479	EFO:1000645

Clinical trials

Total trials: 39.

Phase distribution

Phase	Trials
PHASE2	12
PHASE3	7
PHASE4	5
PHASE1/PHASE2	5
PHASE1	5
Not specified	3
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02586623	PHASE4	COMPLETED	Sustained Effect of Droxidopa in Symptomatic Neurogenic Orthostatic Hypotension
NCT03034564	PHASE4	TERMINATED	A Randomized, Double-Blind, Placebo-Controlled Study of Droxidopa for Fatigue in Parkinson’s Disease
NCT03115827	PHASE4	COMPLETED	Norepinephrine-targeted Therapy for Action Control in Parkinson Disease
NCT03229174	PHASE4	COMPLETED	Brain Perfusion & Oxygenation in Parkinson’s Disease With NOH
NCT03602014	PHASE4	COMPLETED	Dose Response to the Norepinephrine Precursor Droxidopa in Hypotensive Individuals With Spinal Cord Injury
NCT00581477	PHASE2/PHASE3	TERMINATED	Treatment of Orthostatic Hypotension
NCT00633880	PHASE3	COMPLETED	Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH)
NCT00738062	PHASE3	COMPLETED	Open-Label Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH)
NCT00782340	PHASE3	COMPLETED	A Clinical Study for Patients With Neurogenic Orthostatic Hypotension (NOH) Using Droxidopa
NCT01132326	PHASE3	COMPLETED	Clinical Study of Droxidopa in Patients With Neurogenic Orthostatic Hypotension (NOH) (Droxi-304)
NCT01176240	PHASE3	COMPLETED	A Two Part Study (306A/306B) to Assess Droxidopa in Treatment of NOH in Patients With Parkinson’s Disease
NCT01612078	PHASE3	TERMINATED	Phase 3 Study to Evaluate the Efficacy and Safety of Droxidopa on Orthostatic Hypotension Treatment in Hemodialysis Patients
NCT01927055	PHASE3	TERMINATED	A Clinical Study of Patients With Symptomatic NOH to Assess Sustained Effects of Droxidopa Therapy
NCT02071459	PHASE2/PHASE3	COMPLETED	Efficacy of L-threo DOPS on Orthostatic Hypotension Symptoms and Other Non-motor Symptoms in Patients With MSA
NCT01370512	PHASE2	ENROLLING_BY_INVITATION	Droxidopa / Pyridostigmine in Orthostatic Hypotension
NCT06937307	PHASE2	RECRUITING	Droxidopa to Increase Mean Arterial Pressure in Decompensated Cirrhosis Patients With Acute Kidney Injury
NCT07398508	PHASE1/PHASE2	RECRUITING	Phase I/II Study of NORTHERA (DROXIDOPA) for Dysautonomia in Pediatric Survivors of Menkes Disease.
NCT00547911	PHASE1/PHASE2	TERMINATED	Augmenting Effects of L-DOPS With Carbidopa and Entacapone
NCT00657046	PHASE2	COMPLETED	Safety and Benefit Study of Droxidopa to Treat Patients With Intradialytic Hypotension
NCT00977171	PHASE2	TERMINATED	Study To Assess The Clinical Benefit Of Droxidopa In Subjects With Chronic Fatigue Syndrome
NCT00983814	PHASE2	COMPLETED	Study of Droxidopa Treatment in Adults With Attention Deficit Hyperactivity Disorder With Co-administration of Carbidopa
NCT01323374	PHASE2	COMPLETED	Study To Assess The Clinical Benefit Of Droxidopa And Droxidopa/Carbidopa In Subjects With Fibromyalgia
NCT01331122	PHASE1/PHASE2	WITHDRAWN	Study to Assess Droxidopa in the Treatment of Freezing Of Gait Symptoms in Patients With Parkinson’s Disease
NCT02066571	PHASE2	UNKNOWN	Study to Assess the Clinical Benefit and Safety of Droxidopa in Parkinson’s Disease
NCT02558972	PHASE2	TERMINATED	Northera Improves Postural Tachycardia Syndrome (POTS) and Postural Vasovagal Syncope (VVS)
NCT02624310	PHASE2	WITHDRAWN	A Study of Norepinephrine in Patients With Congenital Insensitivity to Pain and Anhidrosis
NCT02812147	PHASE2	UNKNOWN	Effect of L-Dihydoxyphenylserine on Locomotion, Postural Stability, and Fall Risk Reduction in Parkinson Disease
NCT03070730	PHASE1/PHASE2	TERMINATED	Hemodynamic Response of Neuropathic And Non-Neuropathic POTS Patients To Adrenoreceptor Agonist And Antagonist
NCT03446807	PHASE2	WITHDRAWN	Safety and Efficacy of Droxidopa for Fatigue in Patients With Parkinsonism
NCT03567447	PHASE2	UNKNOWN	Effect of L-Dihydroxyphenylserine (L-DOPS) on Falls in Patients With Neurogenic Orthostatic Hypotension (NOH)
NCT04977388	PHASE1/PHASE2	COMPLETED	NORTHERA (DROXIDOPA) for Dysautonomia in Adult Survivors of Menkes Disease and Occipital Horn Syndrome
NCT02897063	PHASE1	RECRUITING	Effects of Midodrine and Droxidopa on Splanchnic Capacitance in Autonomic Failure
NCT01149629	PHASE1	COMPLETED	Study of the Fed-Fast Pharmocokinetics and Bioequivalance of 300mg Capsules of Droxidopa
NCT01327066	PHASE1	COMPLETED	Electrocardiographic (ECG) Safety Study of Droxidopa at Clinical and Supratherapeutic Dose
NCT01354158	PHASE1	COMPLETED	A Dose Titration of Droxidopa in Patients With Spinal Cord Injury
NCT01468259	PHASE1	WITHDRAWN	A Multi-Center, Open-Label Study
NCT00004478	Not specified	COMPLETED	Droxidopa in Treating Patients With Neurogenic Hypotension
NCT00889135	Not specified	APPROVED_FOR_MARKETING	Long Term Treatment With L-DOPS
NCT03173781	Not specified	COMPLETED	Effects of Droxidopa When Measuring Gait Speed, Kyphosis, and Functional Reach in Parkinson’s Disease

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

439 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	CHRM1
LINAGLIPTIN	ChEMBL + PubChem	Phase 4 (approved)	CHRM1
PIMAVANSERIN	ChEMBL + PubChem	Phase 4 (approved)	CHRM1
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	CHRM1
VORAPAXAR	ChEMBL + PubChem	Phase 4 (approved)	CHRM1
ACETYLCHOLINE	ChEMBL	Phase 4 (approved)	CHRM1
ACETYLCHOLINE CHLORIDE	ChEMBL	Phase 4 (approved)	CHRM1
ACLIDINIUM BROMIDE	ChEMBL	Phase 4 (approved)	CHRM1
AMBENONIUM	ChEMBL	Phase 4 (approved)	CHRM1
AMDINOCILLIN PIVOXIL	ChEMBL	Phase 4 (approved)	CHRM1
AMIODARONE	ChEMBL	Phase 4 (approved)	CHRM1
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	CHRM1
AMLODIPINE	ChEMBL	Phase 4 (approved)	CHRM1
AMODIAQUINE	ChEMBL	Phase 4 (approved)	CHRM1
AMOROLFINE	ChEMBL	Phase 4 (approved)	CHRM1
AMOXAPINE	ChEMBL	Phase 4 (approved)	CHRM1
AMSACRINE	ChEMBL	Phase 4 (approved)	CHRM1
ANISOTROPINE	ChEMBL	Phase 4 (approved)	CHRM1
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	CHRM1
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	CHRM1
ATOMOXETINE	ChEMBL	Phase 4 (approved)	CHRM1
ATROPINE	ChEMBL	Phase 4 (approved)	CHRM1
AZATADINE	ChEMBL	Phase 4 (approved)	CHRM1
AZELASTINE	ChEMBL	Phase 4 (approved)	CHRM1
BALSALAZIDE	ChEMBL	Phase 4 (approved)	CHRM1
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	CHRM1
BECLOMETHASONE DIPROPIONATE	ChEMBL	Phase 4 (approved)	CHRM1
BENPERIDOL	ChEMBL	Phase 4 (approved)	CHRM1
BENZTROPINE	ChEMBL	Phase 4 (approved)	CHRM1
BENZYDAMINE	ChEMBL	Phase 4 (approved)	CHRM1
BEPRIDIL	ChEMBL	Phase 4 (approved)	CHRM1
BETAMETHASONE PHOSPHORIC ACID	ChEMBL	Phase 4 (approved)	CHRM1
BETHANECHOL	ChEMBL	Phase 4 (approved)	CHRM1
BEXAROTENE	ChEMBL	Phase 4 (approved)	CHRM1
BIPERIDEN	ChEMBL	Phase 4 (approved)	CHRM1
BITHIONOL	ChEMBL	Phase 4 (approved)	CHRM1
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	CHRM1
BROMODIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	CHRM1
BROMPERIDOL	ChEMBL	Phase 4 (approved)	CHRM1
BROMPHENIRAMINE	ChEMBL	Phase 4 (approved)	CHRM1
BUDESONIDE	ChEMBL	Phase 4 (approved)	CHRM1
BUTRIPTYLINE	ChEMBL	Phase 4 (approved)	CHRM1
CABOZANTINIB	ChEMBL	Phase 4 (approved)	CHRM1
CARBACHOL	ChEMBL	Phase 4 (approved)	CHRM1
CARBAMOYLCHOLINE	ChEMBL	Phase 4 (approved)	CHRM1
CARBETAPENTANE	ChEMBL	Phase 4 (approved)	CHRM1
CARIPRAZINE	ChEMBL	Phase 4 (approved)	CHRM1
CASPOFUNGIN	ChEMBL	Phase 4 (approved)	CHRM1
CERIVASTATIN	ChEMBL	Phase 4 (approved)	CHRM1
CEVIMELINE	ChEMBL	Phase 4 (approved)	CHRM1
CHLORMADINONE	ChEMBL	Phase 4 (approved)	CHRM1
CHLOROQUINE	ChEMBL	Phase 4 (approved)	CHRM1
CHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	CHRM1
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	CHRM1
CHLORPROTHIXENE	ChEMBL	Phase 4 (approved)	CHRM1
CICLOPIROX	ChEMBL	Phase 4 (approved)	CHRM1
CINACALCET	ChEMBL	Phase 4 (approved)	CHRM1
CINNARIZINE	ChEMBL	Phase 4 (approved)	CHRM1
CITALOPRAM	ChEMBL	Phase 4 (approved)	CHRM1
CLEMASTINE	ChEMBL	Phase 4 (approved)	CHRM1