Physostigmine

Summary

Physostigmine (CHEMBL94) is an approved small-molecule EC 3.1.1.8 (cholinesterase) inhibitor (ATC S01EB05) targeting ACHE and BCHE; indicated across 4 conditions including glaucoma and delirium.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: S01EB05 (+1 more)
• Targets: 2 (ACHE, BCHE)
• Indications: 4 conditions
• Clinical trials: 9
• Chemistry: 275.35 Da · C15H21N3O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL94
Name	Physostigmine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5983
ChEBI	CHEBI:27953
ATC	S01EB05, V03AB19
Molecular formula	C15H21N3O2
Molecular weight	275.35
InChIKey	PIJVFDBKTWXHHD-HIFRSBDPSA-N

SMILES: C[C@@]12CCN([C@@H]1N(C3=C2C=C(C=C3)OC(=O)NC)C)C

IUPAC name: [(3aR,8bS)-3,4,8b-trimethyl-2,3a-dihydro-1H-pyrrolo[2,3-b]indol-7-yl] N-methylcarbamate

Pharmacological roles (ChEBI): miotic, EC 3.1.1.8 (cholinesterase) inhibitor, antidote to curare poisoning.

Also known as: (-)-physostigmine, Cogmine, Eserin, Eserinum, MCV-4484, NSC-30782, Physostigmine, physostigmine, eserine, Eserine, (-)-Physostigmine, SID26753571

Parent form; salt/anhydrous children: CHEMBL338975, CHEMBL537674, CHEMBL2105891

Patent coverage: 4,216 distinct patent families (14,305 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 14,284 (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	7.8	9.6%	P22303
BCHE	butyrylcholinesterase	Inhibition	7.8	0.1%	P06276

Broader ChEMBL bioactivity targets: 22 (assay-derived). Sample: Lysine-specific demethylase 4E, Survival motor neuron protein, Fructose-bisphosphate aldolase, Prelamin-A/C, RecQ-like DNA helicase BLM, Cholinesterase, Acetylcholinesterase, Prostaglandin G/H synthase 1, Mu-type opioid receptor, Kappa-type opioid receptor.

Bioactivity

ChEMBL activities: 144 potent at pChembl ≥ 5 of 157 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ACHE	9.37	IC50	0.43	nM	CHEMBL_ACT_1096070
P37136	9.17	IC50	0.68	nM	CHEMBL_ACT_1189595
P21836	9.17	IC50	0.68	nM	CHEMBL_ACT_98616
P21836	9.16	IC50	0.69	nM	CHEMBL_ACT_496010
O42275	9	IC50	1	nM	CHEMBL_ACT_1278530
P37136	9	IC50	1	nM	CHEMBL_ACT_3206173
P37136	8.7	IC50	2	nM	CHEMBL_ACT_769531
ACHE	8.54	IC50	2.9	nM	CHEMBL_ACT_13371835
O42275	8.52	IC50	3	nM	CHEMBL_ACT_19306868
LMNA	8.4	Potency	4	nM	CHEMBL_ACT_3641875
O42275	8.11	IC50	7.7	nM	CHEMBL_ACT_14671241
O42275	8.11	IC50	7.8	nM	CHEMBL_ACT_19307215
P37136	7.96	IC50	11	nM	CHEMBL_ACT_10961334
P04058	7.96	IC50	11	nM	CHEMBL_ACT_14746316
ACHE	7.87	IC50	13.49	nM	CHEMBL_ACT_1840520
ACHE	7.85	IC50	14.13	nM	CHEMBL_ACT_117580
P81908	7.85	IC50	14	nM	CHEMBL_ACT_14746350
ACHE	7.85	IC50	14.1	nM	CHEMBL_ACT_683107
P37136	7.85	IC50	14	nM	CHEMBL_ACT_769529
BCHE	7.82	IC50	15	nM	CHEMBL_ACT_350519
BCHE	7.8	IC50	16	nM	CHEMBL_ACT_1413695
BCHE	7.8	IC50	16	nM	CHEMBL_ACT_1699449
BCHE	7.8	IC50	16	nM	CHEMBL_ACT_226310
ACHE	7.8	IC50	16	nM	CHEMBL_ACT_24400428
BCHE	7.8	IC50	16	nM	CHEMBL_ACT_24400559
BCHE	7.8	IC50	16	nM	CHEMBL_ACT_24963155
BCHE	7.8	IC50	16	nM	CHEMBL_ACT_3370607
BCHE	7.8	IC50	16	nM	CHEMBL_ACT_454432
BCHE	7.8	IC50	16	nM	CHEMBL_ACT_731682
ACHE	7.75	IC50	17.78	nM	CHEMBL_ACT_728065

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

4 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
glaucoma	4	MONDO:0005041	MONDO:0005041
delirium	3	MONDO:0045057	EFO:0009267

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

Clinical trials

Total trials: 9.

Phase distribution

Phase	Trials
Not specified	5
PHASE3	2
PHASE4	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03090620	PHASE4	COMPLETED	Treatment of Adolescent Antimuscarinic (Anticholinergic) Toxidrome
NCT01394445	PHASE3	COMPLETED	Pilot Study of Physostigmine-Enhanced Opioid Analgesia
NCT02216266	PHASE3	UNKNOWN	Evaluation if Physostigmine Reduces Symptoms in Patients Who Has Developed a Delirium in Intensive Care After a Surgery
NCT00689208	EARLY_PHASE1	COMPLETED	Pharmacological Intervention in Insulin Resistance Targeting Autonomic Nerve Activity
NCT00850850	Not specified	UNKNOWN	Physostigmine After General Anesthesia
NCT01121497	Not specified	UNKNOWN	The Effect of Physostigmine on Cognitive Functioning in the Immediate Period After Sedation for Colonoscopy
NCT01171118	Not specified	COMPLETED	Phamacological Reversal of Airway Instability During Sedation
NCT02008292	Not specified	COMPLETED	Acetylcholine, Tobacco Smoking, Genes and Nicotinic Receptors
NCT03013322	Not specified	COMPLETED	Anticholium® Per Se

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.

155 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
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
RIVASTIGMINE	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
ISOFLUROPHATE	ChEMBL	Phase 4 (approved)	ACHE