Rivastigmine

Summary

Rivastigmine (CHEMBL636) is an approved small-molecule EC 3.1.1.8 (cholinesterase) inhibitor (ATC N06DA03) targeting ACHE and BCHE; indicated across 18 conditions including dementia and alzheimer disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N06DA03
• Targets: 2 (ACHE, BCHE)
• Indications: 18 conditions
• Clinical trials: 70
• Chemistry: 250.34 Da · C14H22N2O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL636
Name	Rivastigmine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	77991
ChEBI	CHEBI:8874
ATC	N06DA03
Molecular formula	C14H22N2O2
Molecular weight	250.34
InChIKey	XSVMFMHYUFZWBK-NSHDSACASA-N

SMILES: CCN(C)C(=O)OC1=CC=CC(=C1)[C@H](C)N(C)C

IUPAC name: [3-[(1S)-1-(dimethylamino)ethyl]phenyl] N-ethyl-N-methylcarbamate

ChEBI definition: A carbamate ester obtained by formal condensation of the carboxy group of ethyl(methyl)carbamic acid with the phenolic OH group of 3-[(1S)-1-(dimethylamino)ethyl]phenol. A reversible cholinesterase inhibitor.

Pharmacological roles (ChEBI): EC 3.1.1.8 (cholinesterase) inhibitor, neuroprotective agent, cholinergic drug.

Also known as: ENA-713, ENA-713D, Exelon, ONO-2540, Rivastigmina, Rivastigmine, Rivastigmine 3m health care ltd, SDZ-212713, SDZ-ENA-713, rivastigmine, RIVASTIGMINE, SID174006853

Parent form; salt/anhydrous children: CHEMBL1201092, CHEMBL3187096

Patent coverage: 8,207 distinct patent families (30,156 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 30,153 (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
ACHE	acetylcholinesterase (Yt blood group)	Inhibition	5.4	9.6%	P22303
BCHE	butyrylcholinesterase	Inhibition	7.4	0.1%	P06276

Broader ChEMBL bioactivity targets: 11 (assay-derived). Sample: Cholinesterase, Acetylcholinesterase, Fatty-acid amide hydrolase 1, Cholinesterase, Acetylcholinesterase, Acetylcholinesterase, Acetylcholinesterase, Cholinesterase, Acetylcholinesterase, Acetylcholine receptor subunit epsilon.

Bioactivity

ChEMBL activities: 156 potent at pChembl ≥ 5 of 189 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
BCHE	7.84	IC50	14.3	nM	CHEMBL_ACT_23213229
BCHE	7.52	IC50	30	nM	CHEMBL_ACT_15133449
BCHE	7.52	IC50	30	nM	CHEMBL_ACT_18793816
BCHE	7.52	IC50	30.1	nM	CHEMBL_ACT_1924056
BCHE	7.43	IC50	37	nM	CHEMBL_ACT_1413723
BCHE	7.43	IC50	37	nM	CHEMBL_ACT_1699433
BCHE	7.43	IC50	37	nM	CHEMBL_ACT_22916038
BCHE	7.43	IC50	37	nM	CHEMBL_ACT_29108575
BCHE	7.43	IC50	37	nM	CHEMBL_ACT_2989546
ACHE	7.43	IC50	37	nM	CHEMBL_ACT_6217813
ACHE	7.43	IC50	37	nM	CHEMBL_ACT_6217823
BCHE	7.43	IC50	37	nM	CHEMBL_ACT_839078
BCHE	7.31	IC50	49	nM	CHEMBL_ACT_6180558
P81908	7.28	IC50	52	nM	CHEMBL_ACT_26135043
ACHE	7.27	IC50	54	nM	CHEMBL_ACT_15762382
ACHE	7.27	IC50	54	nM	CHEMBL_ACT_6180551
Q03311	7.24	IC50	58	nM	CHEMBL_ACT_19449693
P81908	7.24	IC50	58	nM	CHEMBL_ACT_23258115
ACHE	7.22	IC50	60	nM	CHEMBL_ACT_23213208
BCHE	7.04	IC50	91	nM	CHEMBL_ACT_29075101
P81908	7.04	IC50	91	nM	CHEMBL_ACT_29133713
BCHE	6.98	IC50	105.3	nM	CHEMBL_ACT_25923099
BCHE	6.77	IC50	170	nM	CHEMBL_ACT_2917522
BCHE	6.76	IC50	172.7	nM	CHEMBL_ACT_29217721
BCHE	6.75	IC50	179	nM	CHEMBL_ACT_6218761
BCHE	6.58	IC50	260	nM	CHEMBL_ACT_15068004
BCHE	6.58	IC50	260	nM	CHEMBL_ACT_17966791
BCHE	6.52	IC50	301	nM	CHEMBL_ACT_10941495
BCHE	6.52	IC50	300	nM	CHEMBL_ACT_12633734
BCHE	6.52	IC50	300	nM	CHEMBL_ACT_13922775

Target pathways

Aggregated over 2 target gene(s): ACHE, BCHE.

Top Reactome pathways

12 total, by targets touching each:

Pathway	Targets	Genes
Neurotransmitter clearance	2	ACHE, BCHE
Synthesis of PC	2	ACHE, BCHE
Synthesis, secretion, and deacylation of Ghrelin	2	ACHE, BCHE
Transmission across Chemical Synapses	1	ACHE
Neuronal System	1	ACHE
Metabolism	1	ACHE
Glycerophospholipid biosynthesis	1	ACHE
Phospholipid metabolism	1	ACHE
Peptide hormone metabolism	1	ACHE
Metabolism of proteins	1	ACHE
Metabolism of lipids	1	ACHE
Aspirin ADME	1	BCHE

Dominant GO biological processes

GO term	Targets
acetylcholine catabolic process	2
acetylcholine catabolic process in synaptic cleft	1
regulation of receptor recycling	1
osteoblast development	1
cell adhesion	1
nervous system development	1
synapse assembly	1
receptor internalization	1
negative regulation of synaptic transmission, cholinergic	1
amyloid precursor protein metabolic process	1
positive regulation of protein secretion	1
retina development in camera-type eye	1
acetylcholine receptor signaling pathway	1
positive regulation of cold-induced thermogenesis	1
xenobiotic metabolic process	1

Indications & clinical

Indications

18 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
dementia	4	MONDO:0001627	HP:0000726
Alzheimer disease	4	MONDO:0004975	MONDO:0004975
Parkinson disease	4	MONDO:0005180	MONDO:0005180
vascular dementia	3	MONDO:0004648	EFO:0004718
anxiety	3	MONDO:0011918	EFO:0005230
delirium	3	MONDO:0045057	EFO:0009267
brain injury	3	MONDO:0043510	MONDO:0043510
depressive disorder	3	MONDO:0002050	MONDO:0002050
progressive supranuclear palsy	3	MONDO:0019037	MONDO:0019037
Down syndrome	1	MONDO:0008608	EFO:0001064
methamphetamine dependence	1	MONDO:0005419	EFO:0004701
drug dependence	1	MONDO:0005303	EFO:0003890
substance-related disorder	1	MONDO:0002494	MONDO:0002491
central nervous system disorder	1	MONDO:0002602	EFO:0009386

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

Clinical trials

Total trials: 70.

Phase distribution

Phase	Trials
PHASE4	28
PHASE3	20
Not specified	9
PHASE1	6
PHASE2	5
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05768126	PHASE4	RECRUITING	Prediction of ECT Treatment Response and Reduction of Cognitive Side-effects Using EEG and Rivastigmine
NCT00018278	PHASE4	COMPLETED	Electrophysiologic Measures of Treatment Response in Alzheimer Disease
NCT00102284	PHASE4	TERMINATED	Neuromodulation and Language Acquisition (Project Stage Ia)
NCT00102856	PHASE4	SUSPENDED	Neuromodulation and Language Acquisition (Stage Ib)
NCT00104442	PHASE4	COMPLETED	Study of the Effects of Current Drug Treatments on Levels of Certain Brain Chemicals in Alzheimer’s Disease
NCT00219245	PHASE4	COMPLETED	An Extension Study Evaluating the Efficacy and Safety of Rivastigmine in Patients With Traumatic Brain Injury (TBI) With Persistent Cognitive Deficits
NCT00234637	PHASE4	COMPLETED	Rivastigmine Monotherapy and Combination Therapy With Memantine in Patients With Moderately Severe Alzheimer’s Disease Who Failed to Benefit From Previous Cholinesterase Inhibitor Treatment
NCT00305903	PHASE4	COMPLETED	Safety and Tolerability of Rivastigmine With Add-on Memantine in Patients With Probable Alzheimer’s Disease
NCT00561392	PHASE4	COMPLETED	Clinical Effectiveness of 10 cm^2 Rivastigmine Patch in Patients With Alzheimer’s Disease
NCT00622713	PHASE4	COMPLETED	A 24 Week, Multicenter, Open, Evaluation of the Clinical Effectiveness of the Once-daily 10 cm^2 Rivastigmine Patch Formulation in Patients With Probable Alzheimer’s Disease (EXTRA)
NCT00669344	PHASE4	COMPLETED	RIVastigmine In Vascular cognitivE Impairment
NCT00704301	PHASE4	TERMINATED	Rivastigmine for Intensive Care Unit (ICU) Delirium
NCT00731224	PHASE4	COMPLETED	Compliance and Tolerability of Rivastigmine Transdermal Patch 10 cm² in Patients With Probable Alzheimer’s Disease.
NCT00835159	PHASE4	COMPLETED	Rivastigmine in the Treatment of Postoperative Delirium: a Pilot Clinical Trial
NCT00881205	PHASE4	TERMINATED	Rivastigmine in Multiple Sclerosis Patients With Cognitive Impairment
NCT00948766	PHASE4	COMPLETED	Effects of Rivastigmine Patch on Activities of Daily Living and Cognition in Patients With Severe Dementia of the Alzheimer’s Type (ACTION) (Study Protocol CENA713DUS44, NCT00948766) and a 24 Week Open-label Extension to Study CENA713DUS44
NCT01025466	PHASE4	COMPLETED	Exelon Patch and Combination With Memantine Comparative Trial
NCT01047579	PHASE4	COMPLETED	A 12 Week, Multicenter, Open Label Evaluation of Caregiver Preference, Safety and Tolerability of Exelon® Patch (Rivastigmine Transdermal) in Patients With Alzheimer’s Disease
NCT01340885	PHASE4	COMPLETED	Cognitive Decline in Non-demented PD
NCT01348282	PHASE4	COMPLETED	Efficacy and Safety of Two Pharmacologic Strategies on Neurocognitive Impairment in HIV Infection. The TRIANT-TE Study
NCT01529619	PHASE4	COMPLETED	Efficacy, Safety and Tolerability of Rivastigmine Patch in Patients With Mild to Moderate Alzheimer’s Disease Switched From Cholinesterase Inhibitors
NCT01856738	PHASE4	TERMINATED	Cholinesterase Inhibitors to Slow Progression of Visual Hallucinations in Parkinson’s Disease
NCT02413554	PHASE4	COMPLETED	Rivastigmine Patch Effect on the Post-operative Delirium in Patients at Risk of Dementia.
NCT02444637	PHASE4	COMPLETED	Open Label Trial of Rivastigmine Patch in Subjects With Mild to Moderate Stage AD Having Coexisting svCVD
NCT02703636	PHASE4	COMPLETED	NextStep:Study to Evaluate Safety,Efficacy & Tolerability of Rivastigmine Patch in Mild to Moderate Alzheimer’s Patients.
NCT02989402	PHASE4	COMPLETED	A Phase IV Study to Evaluate Safety, Tolerability and Effectiveness of Rivastigmine Patch 15cm2 in Patients With Severe Dementia of the Alzheimer’s Type.
NCT03840837	PHASE4	COMPLETED	Cholinergic Neurotransmission in Mobility and Cognition in Parkinson Disease
NCT07545382	PHASE4	COMPLETED	Rivastigmine as an Antidote for Clozapine and Other Anticholinergic-Induced CNS Depression and Delirium: A Study of 100 Cases
NCT00000174	PHASE3	COMPLETED	Investigation Into Delay to Diagnosis of Alzheimer’s Disease With Exelon (InDDEx)
NCT00099216	PHASE3	COMPLETED	Efficacy and Safety of Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00099242	PHASE3	COMPLETED	Efficacy and Safety of the Rivastigmine Transdermal Patch in Patients With Probable Alzheimer’s Disease
NCT00130338	PHASE3	COMPLETED	Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00134953	PHASE3	TERMINATED	Efficacy and Safety of Rivastigmine in Patients With Mild Cognitive Impairment
NCT00171795	PHASE3	COMPLETED	Efficacy and Safety of Rivastigmine in Patients With Traumatic Brain Injury and Cognitive Impairment
NCT00219232	PHASE3	COMPLETED	An Open-label Extension to Evaluate the Efficacy and Safety of the Rivastigmine Transdermal Patch in Patients With Probable Alzheimer’s Disease
NCT00423085	PHASE3	COMPLETED	Efficacy and Safety of Rivastigmine Transdermal Patch in Patients With Mild to Moderate Alzheimer’s Disease
NCT00428389	PHASE3	COMPLETED	Safety of Switching From Donepezil to Rivastigmine Patch in Patients With Probable Alzheimer’s Disease
NCT00506415	PHASE3	COMPLETED	Comparative Efficacy, Safety, and Tolerability of Rivastigmine 10 and 15 cm^2 Patch in Patients With Alzheimer’s Disease (AD) Showing Cognitive Decline
NCT00599287	PHASE3	TERMINATED	Methylphenidate, Rivastigmine or Haloperidol in Hypoactive Delirium in Intensive Care Patients
NCT00623103	PHASE3	COMPLETED	Long-term Safety of Rivastigmine Capsule and Patch in Patients With Mild to Moderately-severe Dementia Associated With Parkinson’s Disease (PDD)

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 5 clinical and 38 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

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

Molecule	Source	Status	Shared targets
BERBERINE	ChEMBL	Phase 4 (approved)	ACHE, BCHE
DONEPEZIL	ChEMBL	Phase 4 (approved)	ACHE, BCHE
ETHOPROPAZINE	ChEMBL	Phase 4 (approved)	ACHE, BCHE
GALANTAMINE	ChEMBL	Phase 4 (approved)	ACHE, BCHE
NEOSTIGMINE	ChEMBL	Phase 4 (approved)	ACHE, BCHE
NEOSTIGMINE METHYLSULFATE	ChEMBL	Phase 4 (approved)	ACHE, BCHE
PHYSOSTIGMINE	ChEMBL	Phase 4 (approved)	ACHE, BCHE
PHYSOSTIGMINE SALICYLATE	ChEMBL	Phase 4 (approved)	ACHE, BCHE
PYRIDOSTIGMINE	ChEMBL	Phase 4 (approved)	ACHE, BCHE
PYRIDOSTIGMINE BROMIDE	ChEMBL	Phase 4 (approved)	ACHE, BCHE
RASAGILINE	ChEMBL	Phase 4 (approved)	ACHE, BCHE
RESERPINE	ChEMBL	Phase 4 (approved)	ACHE, BCHE
TACRINE	ChEMBL	Phase 4 (approved)	ACHE, BCHE
BAMBUTEROL	ChEMBL	Phase 3	ACHE, BCHE
EBSELEN	ChEMBL	Phase 3	ACHE, BCHE
LATREPIRDINE	ChEMBL	Phase 3	ACHE, BCHE
QUERCETIN	ChEMBL	Phase 3	ACHE, BCHE
EPTASTIGMINE	ChEMBL	Phase 2	ACHE, BCHE
ESERIDINE	ChEMBL	Phase 2	ACHE, BCHE
FISETIN	ChEMBL	Phase 2	ACHE, BCHE
GANSTIGMINE	ChEMBL	Phase 2	ACHE, BCHE
HUPERZINE A	ChEMBL	Phase 2	ACHE, BCHE
ICOPEZIL	ChEMBL	Phase 2	ACHE, BCHE
NEOSTIGMINE BROMIDE	ChEMBL	Phase 2	ACHE, BCHE
PHENOTHIAZINE	ChEMBL	Phase 2	ACHE, BCHE
SANGUINARIUM	ChEMBL	Phase 2	ACHE, BCHE
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	ACHE
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	ACHE
TADALAFIL	ChEMBL + PubChem	Phase 4 (approved)	ACHE
ALFUZOSIN	ChEMBL	Phase 4 (approved)	ACHE
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	ACHE
BOSUTINIB	ChEMBL	Phase 4 (approved)	ACHE
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	ACHE
BUTENAFINE	ChEMBL	Phase 4 (approved)	ACHE
CABERGOLINE	ChEMBL	Phase 4 (approved)	ACHE
CAFFEINE	ChEMBL	Phase 4 (approved)	ACHE
CANNABIDIOL	ChEMBL	Phase 4 (approved)	ACHE
CITALOPRAM	ChEMBL	Phase 4 (approved)	ACHE
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	ACHE
DECAMETHONIUM	ChEMBL	Phase 4 (approved)	ACHE
DECAMETHONIUM BROMIDE	ChEMBL	Phase 4 (approved)	ACHE
DEQUALINIUM	ChEMBL	Phase 4 (approved)	ACHE
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	ACHE
DISULFIRAM	ChEMBL	Phase 4 (approved)	ACHE
DOFETILIDE	ChEMBL	Phase 4 (approved)	ACHE
DYCLONINE	ChEMBL	Phase 4 (approved)	ACHE
EBASTINE	ChEMBL	Phase 4 (approved)	ACHE
ECONAZOLE	ChEMBL	Phase 4 (approved)	ACHE
EDROPHONIUM	ChEMBL	Phase 4 (approved)	ACHE
EDROPHONIUM CHLORIDE	ChEMBL	Phase 4 (approved)	ACHE
EPIRUBICIN	ChEMBL	Phase 4 (approved)	ACHE
ETHYLESTRENOL	ChEMBL	Phase 4 (approved)	ACHE
FENOFIBRATE	ChEMBL	Phase 4 (approved)	ACHE
FLAVOXATE	ChEMBL	Phase 4 (approved)	ACHE
FLUOXETINE	ChEMBL	Phase 4 (approved)	ACHE
GALLAMINE	ChEMBL	Phase 4 (approved)	ACHE
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	ACHE
HEXAFLUORENIUM	ChEMBL	Phase 4 (approved)	ACHE
ILOPERIDONE	ChEMBL	Phase 4 (approved)	ACHE
IRINOTECAN	ChEMBL	Phase 4 (approved)	ACHE