Methoxamine

Summary

Methoxamine (CHEMBL524) is an approved small-molecule antihypotensive agent (ATC C01CA10) targeting ADRA1A, ADRA1B, and ADRA1D; indicated across 3 conditions including cardiovascular disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C01CA10
• Targets: 3 (ADRA1A, ADRA1B, ADRA1D)
• Indications: 3 conditions
• Clinical trials: 7
• Chemistry: 211.26 Da · C11H17NO3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL524
Name	Methoxamine
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	6082
ChEBI	CHEBI:6839
ATC	C01CA10
Molecular formula	C11H17NO3
Molecular weight	211.26
InChIKey	WJAJPNHVVFWKKL-UHFFFAOYSA-N

SMILES: CC(C(C1=C(C=CC(=C1)OC)OC)O)N

IUPAC name: 2-amino-1-(2,5-dimethoxyphenyl)propan-1-ol

ChEBI definition: An amphetamine in which the parent 1-phenylpropan-2-amine skeleton is substituted at position 1 with an hydroxy group and the phenyl ring is 2- and 5-substituted with methoxy groups. It is an antihypotensive agent (pressor), an agonist acting directly at α-adrenoceptors with selectivity for the α-1 adrenoceptor subtype similar to phenylephrine .

Pharmacological roles (ChEBI): antihypotensive agent, α-adrenergic agonist.

Also known as: Methoxamine, Metoxamina, NRL-001, Nrl001, NRL001, SID90341132, METHOXAMINE, METHOXAMINE HYDROCHLORIDE, methoxamine

Parent form; salt/anhydrous children: CHEMBL1201103

Patent coverage: 1,632 distinct patent families (4,643 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 4,642 (100%) 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
ADRA1A	α1A-adrenoceptor	Full agonist	8.1		P35348
ADRA1B	α1B-adrenoceptor	Partial agonist	4	0%	P35368
ADRA1D	α1D-adrenoceptor	Full agonist	4.9	0.2%	P25100

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Alpha-2A adrenergic receptor, Adrenergic receptor alpha-2, Alpha-1A adrenergic receptor.

Bioactivity

ChEMBL activities: 3 potent at pChembl ≥ 5 of 4 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ADRA1A	7.68	AC50	21	nM	CHEMBL_ACT_25209063
ADRA1A	6.14	EC50	720	nM	CHEMBL_ACT_334115
P19328	5.44	IC50	3600	nM	CHEMBL_ACT_172765

Target pathways

Aggregated over 3 target gene(s): ADRA1A, ADRA1B, ADRA1D.

Top Reactome pathways

9 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	3	ADRA1A, ADRA1B, ADRA1D
Signaling by GPCR	3	ADRA1A, ADRA1B, ADRA1D
Class A/1 (Rhodopsin-like receptors)	3	ADRA1A, ADRA1B, ADRA1D
Amine ligand-binding receptors	3	ADRA1A, ADRA1B, ADRA1D
GPCR downstream signalling	3	ADRA1A, ADRA1B, ADRA1D
Adrenoceptors	3	ADRA1A, ADRA1B, ADRA1D
G alpha (q) signalling events	3	ADRA1A, ADRA1B, ADRA1D
G alpha (12/13) signalling events	3	ADRA1A, ADRA1B, ADRA1D
GPCR ligand binding	3	ADRA1A, ADRA1B, ADRA1D

Dominant GO biological processes

GO term	Targets
signal transduction	3
G protein-coupled receptor signaling pathway	3
phospholipase C-activating G protein-coupled receptor signaling pathway	3
positive regulation of cytosolic calcium ion concentration	3
cell-cell signaling	3
positive regulation of MAPK cascade	3
adenylate cyclase-activating adrenergic receptor signaling pathway	3
neuron-glial cell signaling	3
adrenergic receptor signaling pathway	3
positive regulation of cardiac muscle hypertrophy	2
intracellular signal transduction	2
positive regulation of vasoconstriction	2
regulation of muscle contraction	2
regulation of vasoconstriction	2
regulation of cardiac muscle contraction	2

Indications & clinical

Indications

3 indications (1 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
cardiovascular disorder	4	MONDO:0004995	EFO:0000319

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 7.

Phase distribution

Phase	Trials
PHASE1	7

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00850590	PHASE1	COMPLETED	Study of Escalating Doses of NRL001 Given in Slow-release Rectal Suppositories of Different Weights
NCT00857467	PHASE1	COMPLETED	Study to Investigate Safety and Response to 1 or 2 g Rectal Suppositories Containing 5 or 10 mg NRL001.
NCT00893607	PHASE1	COMPLETED	Effect of Single Doses of 10 mg NRL001 Applied as a Suppository to the Anal Canal or Rectum
NCT01099670	PHASE1	COMPLETED	Safety, Tolerability, Pharmacodynamic and Pharmacokinetics of 7.5, 10, 12.5 or 15 mg NRL001 in a 2 g Suppository for 14 Days
NCT01099683	PHASE1	COMPLETED	Safety, Tolerability, Pharmacodynamic and Pharmacokinetics of a Single Rectal Application of 10 mg NRL001 in Elderly Subjects
NCT01175941	PHASE1	COMPLETED	Effect of 7 Days of Dosing With a 10 mg Rectal Suppository of NRL001in Patients With Faecal Incontinence
NCT01406925	PHASE1	COMPLETED	Safety and Tolerability of a Single Intra-anal Dose of NRL001 in Healthy Volunteers

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

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

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
ALFUZOSIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
AMLODIPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
APRACLONIDINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
ASENAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
ATENOLOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
AZELASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
BRIMONIDINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
BUSPIRONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
CARIPRAZINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
CISAPRIDE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
CLONIDINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
CLOZAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
DEXMEDETOMIDINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
DOPAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
DOXAZOSIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
EBASTINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
EPINEPHRINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
FENOLDOPAM	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
HALOPERIDOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
INDACATEROL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
INDORAMIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
ISOPROTERENOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
LABETALOL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
MOXISYLYTE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
NAFTOPIDIL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
NEFAZODONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
NOREPINEPHRINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
OLANZAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
OXYMETAZOLINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
PHENTOLAMINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
PRAZOSIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
QUETIAPINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
RISPERIDONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
SERTINDOLE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
SILODOSIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
TAMSULOSIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
TEGASEROD	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
TERAZOSIN	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
TERFENADINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
TOLAZOLINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
VERAPAMIL	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
VILAZODONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
XYLOMETAZOLINE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
ZIPRASIDONE	ChEMBL	Phase 4 (approved)	ADRA1A, ADRA1B, ADRA1D
BUNAZOSIN	ChEMBL	Phase 3	ADRA1A, ADRA1B, ADRA1D
IDAZOXAN	ChEMBL	Phase 3	ADRA1A, ADRA1B, ADRA1D
LATREPIRDINE	ChEMBL	Phase 3	ADRA1A, ADRA1B, ADRA1D
MEDETOMIDINE	ChEMBL	Phase 3	ADRA1A, ADRA1B, ADRA1D
YOHIMBINE	ChEMBL	Phase 3	ADRA1A, ADRA1B, ADRA1D
ABANOQUIL	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D
CIRAZOLINE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D
DEXNIGULDIPINE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D
IPSAPIRONE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D
MAZAPERTINE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D
NIGULDIPINE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D
PIPEROXAN	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D
PIZOTYLINE	ChEMBL	Phase 2	ADRA1A, ADRA1B, ADRA1D