Reserpine

Summary

Reserpine (CHEMBL772) is an approved small-molecule antihypertensive agent (ATC C02AA52) targeting SLC18A1 and SLC18A2; indicated across 13 conditions including hypertensive disorder and cerebrovascular disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C02AA52 (+1 more)
• Targets: 2 (SLC18A1, SLC18A2)
• Indications: 13 conditions
• Clinical trials: 7
• Chemistry: 608.7 Da · C33H40N2O9

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL772
Name	Reserpine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5770
ChEBI	CHEBI:28487
ATC	C02AA52, C02AA02
Molecular formula	C33H40N2O9
Molecular weight	608.7
InChIKey	QEVHRUUCFGRFIF-MDEJGZGSSA-N

SMILES: CO[C@H]1[C@@H](C[C@@H]2CN3CCC4=C([C@H]3C[C@@H]2[C@@H]1C(=O)OC)NC5=C4C=CC(=C5)OC)OC(=O)C6=CC(=C(C(=C6)OC)OC)OC

IUPAC name: methyl (1R,15S,17R,18R,19S,20S)-6,18-dimethoxy-17-(3,4,5-trimethoxybenzoyl)oxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate

ChEBI definition: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria.

Pharmacological roles (ChEBI): antihypertensive agent, first generation antipsychotic, adrenergic uptake inhibitor, EC 3.4.21.26 (prolyl oligopeptidase) inhibitor.

Other ChEBI roles (chemical / environmental): environmental contaminant, xenobiotic, plant metabolite.

Also known as: Apoplon, ENT-50146, Hiserpia, NSC-237659, NSC-59272, Rau-sed, Reserpina, Reserpine, Reserpine component of cam-ap-es, Reserpine component of demi-regroton, Reserpine component of diutensen-r, Reserpine component of dralserp

Patent coverage: 202,193 distinct patent families (330,645 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 330,606 (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
SLC18A1	Vesicular monoamine transporter 1	Inhibition	7.45	1%	P54219
SLC18A2	Vesicular monoamine transporter 2	Inhibition	7.9	0%	Q05940

Broader ChEMBL bioactivity targets: 51 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, Lethal(3)malignant brain tumor-like protein 1, Microtubule-associated protein tau, Lysine-specific demethylase 4E, Fructose-bisphosphate aldolase, Prelamin-A/C, RecQ-like DNA helicase BLM, Thrombopoietin, Geminin, Endonuclease 4.

Bioactivity

ChEMBL activities: 57 potent at pChembl ≥ 5 of 105 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
Q27963	9	Ki	1	nM	CHEMBL_ACT_2100955
Q01827	9	AC50	1	nM	CHEMBL_ACT_25197385
Q8BRU6	8.75	IC50	1.79	nM	CHEMBL_ACT_18563548
SLC18A2	8.28	Ki	5.26	nM	CHEMBL_ACT_18563459
SLC18A2	8.1	Kd	8	nM	CHEMBL_ACT_18563503
SLC18A2	7.88	IC50	13.2	nM	CHEMBL_ACT_18563528
SLC18A2	7.81	IC50	15.5	nM	CHEMBL_ACT_24930891
SLC18A1	7.3	IC50	50	nM	CHEMBL_ACT_24930844
ABCB1	7	Ki	100	nM	CHEMBL_ACT_1304210
SLC18A2	6.39	Ki	410	nM	CHEMBL_ACT_18563508
ABCB1	6.3	IC50	500	nM	CHEMBL_ACT_11000874
SLC18A2	6.2	Ki	630	nM	CHEMBL_ACT_18563479
ABCB1	6.01	Ki	970	nM	CHEMBL_ACT_11002312
KCNH2	5.83	AC50	1462	nM	CHEMBL_ACT_25118255
SCN1A	5.8	IC50	1600	nM	CHEMBL_ACT_383642
ACHE	5.77	IC50	1700	nM	CHEMBL_ACT_25527573
OPRM1	5.77	Ki	1686	nM	CHEMBL_ACT_7802524
ABCB1	5.68	IC50	2100	nM	CHEMBL_ACT_11001302
ABCB1	5.68	IC50	2100	nM	CHEMBL_ACT_11001303
ABCB1	5.64	Ki	2310	nM	CHEMBL_ACT_11002749
ABCB1	5.58	IC50	2600	nM	CHEMBL_ACT_11001322
BCHE	5.55	IC50	2800	nM	CHEMBL_ACT_25527579
ABCB1	5.52	IC50	3020	nM	CHEMBL_ACT_2049482
CYP3A4	5.5	Potency	3162	nM	CHEMBL_ACT_4989846
CYP3A4	5.5	Potency	3162	nM	CHEMBL_ACT_5058807
ABCB1	5.49	IC50	3236	nM	CHEMBL_ACT_2049494
ABCB1	5.49	IC50	3236	nM	CHEMBL_ACT_2230322
OPRM1	5.42	AC50	3766	nM	CHEMBL_ACT_25158496
ABCB1	5.41	IC50	3900	nM	CHEMBL_ACT_11001422
CYP3A4	5.4	Potency	3981	nM	CHEMBL_ACT_5006231

Target pathways

Aggregated over 2 target gene(s): SLC18A1, SLC18A2.

Top Reactome pathways

4 total, by targets touching each:

Pathway	Targets	Genes
SLC-mediated transport of neurotransmitters	2	SLC18A1, SLC18A2
Serotonin Neurotransmitter Release Cycle	1	SLC18A2
Norepinephrine Neurotransmitter Release Cycle	1	SLC18A2
Dopamine Neurotransmitter Release Cycle	1	SLC18A2

Dominant GO biological processes

GO term	Targets
aminergic neurotransmitter loading into synaptic vesicle	2
obsolete monoamine transport	2
obsolete dopamine transport	2
serotonin uptake	2
neurotransmitter transport	2
obsolete serotonin transport	2
xenobiotic transport	2
establishment of localization in cell	2
transmembrane transport	2
proton transmembrane transport	2
norepinephrine uptake	1
dopamine uptake	1
response to amphetamine	1
serotonin secretion by mast cell	1
histamine secretion by mast cell	1

Indications & clinical

Indications

13 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
hypertensive disorder	4	MONDO:0005044	EFO:0000537
cerebrovascular disorder	3	MONDO:0011057	EFO:0003763
heart disorder	3	MONDO:0005267	EFO:0003777
atherosclerosis	3	MONDO:0005311	EFO:0003914
coronary artery disorder	3	MONDO:0005010	EFO:0001645
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148
cardiovascular disorder	3	MONDO:0004995	EFO:0000319
cocaine dependence	2	MONDO:0005186	EFO:0002610
drug dependence	2	MONDO:0005303	EFO:0003890
vascular disorder	2	MONDO:0005385	EFO:0004264
pulmonary arterial hypertension	1	MONDO:0015924	EFO:0001361
methamphetamine dependence	1	MONDO:0005419	EFO:0004701

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

Clinical trials

Total trials: 7.

Phase distribution

Phase	Trials
PHASE2	3
PHASE1	2
PHASE3	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00000514	PHASE3	COMPLETED	Systolic Hypertension in the Elderly Program (SHEP)
NCT00000499	PHASE2	COMPLETED	Systolic Hypertension in the Elderly Program (SHEP) (Pilot Study)
NCT00033033	PHASE2	COMPLETED	Reserpine for the Treatment of Cocaine Dependence - 1
NCT03223272	PHASE2	COMPLETED	Mechanisms of Refractory Hypertension (Reserpine)
NCT00267657	PHASE1	UNKNOWN	A Phase 1 Parallel-Group, Double-Blind, Placebo-Controlled Cardiovascular and Behavioral Study Assessing Interactions Between Single Doses of Oral Reserpine and Intravenous Methamphetamine - 1
NCT02684786	PHASE1	WITHDRAWN	A Study of Stellate Ganglion Block and / or Reserpine in Group 2 Pulmonary Hypertension
NCT06199778	Not specified	TERMINATED	Effect of Intermittent Oro-esophageal Tube Feeding on Severe Traumatic Brain Injury Patients With Tracheostomy

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.

5 molecules share ≥1 primary target. Top 5 by shared-target count:

Molecule	Source	Status	Shared targets
Tetrabenazine	ChEMBL + PubChem	Phase 4 (approved)	SLC18A1, SLC18A2
KETANSERIN	ChEMBL	Phase 4 (approved)	SLC18A2
SEROTONIN	ChEMBL + PubChem	Phase 3 (approved)	SLC18A2
FLORBENAZINE	ChEMBL	Phase 2	SLC18A2
LOBELINE	ChEMBL	Phase 2	SLC18A2