physostigmine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
acetylcholinesterase inhibitors 2159 57-47-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • physostigmine
  • cogmine
  • eserine
  • esromiotin
  • (-)-Physostigmine
  • physostigmine salicylate
  • eserine hemisulfate salt
  • eserine hemisulfate
A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity.
  • Molecular weight: 275.35
  • Formula: C15H21N3O2
  • CLOGP: 2.06
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 1
  • TPSA: 44.81
  • ALOGS: -2.44
  • ROTB: 2

Drug dosage:

DoseUnitRoute
0.40 ml None

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.06 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Hosey CM, Chan R, Benet LZ
BA (Bioavailability) 10 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 3.90 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 72 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.64 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1 hours Lombardo F, Berellini G, Obach RS
S (Water solubility) 0.99 mg/mL Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 0.742 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 2.339 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 10.889 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 6.471 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 83.370 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 88.070 % High 1
herg hERG pIC50 4.324 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 2.208 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 4.909 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 82.450 % High 1
kinase-safety-class ACVR2A,ACVR2B,AKT3,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,GRK2,IGF1R,ITK,JAK2,JAK3,MAP2K6,MAP3K21,MAP3K7,MAPK10,MAPK7,MAPKAPK2,MET,NTRK2,PDK2,PDK4,PDPK1,PIM2,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TGFBR1,ZAP70 44
kinase-selectivity-class EIF2AK3,MAP3K7 2
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 4.046 High 1
mh-clint Mouse hepatocyte intrinsic clearance 68.549 High 1
mppb Mouse plasma protein binding (% unbound) 76.890 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 11.169 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 0 High 1
pppb Pig plasma protein binding (% unbound) 87.370 % High 1
rh-clint Rat hepatocyte intrinsic clearance 39.084 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 91.410 % High 1
rppb Rat plasma protein binding (% unbound) 73.810 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 931.108 uM High 1

Approvals:

DateAgencyCompanyOrphan
Jan. 1, 1875 YEAR INTRODUCED

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

None

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Anticholinergic syndrome 103.17 73.10 16 233 4264 110584786

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC S01EB05 SENSORY ORGANS
OPHTHALMOLOGICALS
ANTIGLAUCOMA PREPARATIONS AND MIOTICS
Parasympathomimetics
ATC V03AB19 VARIOUS
ALL OTHER THERAPEUTIC PRODUCTS
ALL OTHER THERAPEUTIC PRODUCTS
Antidotes
MeSH PA D002800 Cholinesterase Inhibitors
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D008916 Miotics
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018678 Cholinergic Agents
CHEBI has role CHEBI:35480 analgesic
CHEBI has role CHEBI:37733 EC 3.1.1.8 (cholinesterase) inhibitor
CHEBI has role CHEBI:39456 antiglaucoma drug
CHEBI has role CHEBI:50864 insulin-sensitizing drug
CHEBI has role CHEBI:51068 miotic
CHEBI has role CHEBI:74530 antidote to curare poisoning

Related Drugs by ATC class:

S01EB Parasympathomimetics 9 drugs
aceclidineacetylcholinecarbacholdemecariumechothiophatefluostigmineneostigmineparaoxonpilocarpine
V03AB Antidotes 28 drugs
4-dimethylaminophenolacetylcysteineamyl nitriteandexanet alfaatropinecopper sulfatedimercaprolethanolflumazenilfomepizoleglutathionehydroxocobalamin show all 28 →

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Open-angle glaucoma indication 84494001 DOID:1067
Anticholinergic Toxicity indication
Secondary glaucoma off-label use 95717004
Angle-closure glaucoma off-label use 392291006 DOID:13550
Hereditary Ataxias off-label use
Keratitis contraindication 5888003 DOID:4677
Urinary tract obstruction contraindication 7163005 DOID:5200
Parkinsonism contraindication 32798002
Gangrene contraindication 36024000
Retinal detachment contraindication 42059000 DOID:5327
Bradycardia contraindication 48867003
Disorder of cardiovascular system contraindication 49601007 DOID:1287
Neuromuscular block, function contraindication 55394004
Iritis contraindication 65074000 DOID:1406
Diabetes mellitus contraindication 73211009 DOID:9351
Epilepsy contraindication 84757009 DOID:1826
Gastrointestinal obstruction contraindication 126765001
Asthma contraindication 195967001 DOID:2841
Anterior uveitis contraindication 410692006 DOID:1407
Pupillary Block Glaucoma contraindication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.89 acidic
pKa2 8.15 Basic
pKa3 2.09 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Acetylcholinesterase Enzyme INHIBITOR IC50 9.37 CHEMBL IUPHAR
Cholinesterase Enzyme Ki 5.30 CHEMBL
Cytochrome P450 2D6 Enzyme IC50 6.70 DRUG MATRIX
Acetylcholinesterase Enzyme IC50 7.96 CHEMBL
Acetylcholinesterase Enzyme IC50 9.17 CHEMBL
Butyrylcholinesterase; Protein Bche Enzyme IC50 8.12 CHEMBL
Acetylcholinesterase Enzyme IC50 9.17 CHEMBL
Acetylcholinesterase Enzyme Ki 7.47 CHEMBL
Acetylcholinesterase Enzyme IC50 7.52 CHEMBL
Muscarinic acetylcholine receptor M1 GPCR IC50 4.43 CHEMBL
Cholinesterase Enzyme IC50 6.55 CHEMBL
Butyrylcholinesterase Enzyme IC50 7.80 CHEMBL
Cholinesterase Enzyme Ki 7.39 CHEMBL
Acetylcholinesterase Enzyme IC50 7.70 CHEMBL

External reference:

IDSource
4019894 VUID
N0000147979 NUI
D00196 KEGG_DRUG
57-64-7 SECONDARY_CAS_RN
4018587 VANDF
4019894 VANDF
C0031849 UMLSCUI
CHEBI:27953 CHEBI
CHEMBL94 ChEMBL_ID
DB00981 DRUGBANK_ID
CHEMBL338975 ChEMBL_ID
D010830 MESH_DESCRIPTOR_UI
5983 PUBCHEM_CID
6598 IUPHAR_LIGAND_ID
9U1VM840SP UNII
33656 RXNORM
1415 MMSL
5296 MMSL
d00342 MMSL
001700 NDDF
001701 NDDF
373347005 SNOMEDCT_US
69050006 SNOMEDCT_US
85429009 SNOMEDCT_US
CHEMBL2105891 ChEMBL_ID
C026718 MESH_SUPPLEMENTAL_RECORD_UI
9U1VM840SP INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Physostigmine Salicylate HUMAN PRESCRIPTION DRUG LABEL 1 17478-510 INJECTION 1 mg INTRAVENOUS unapproved drug other 13 sections
PHYSOSTIGMINE SALICYLATE HUMAN PRESCRIPTION DRUG LABEL 1 51662-1439 INJECTION 1 mg INTRAVENOUS unapproved drug other 13 sections
ANTICHOLIUM HUMAN PRESCRIPTION DRUG LABEL 1 81284-831 INJECTION 0.40 mg INTRAVENOUS Unapproved drug for use in drug shortage 16 sections
ANTICHOLIUM HUMAN PRESCRIPTION DRUG LABEL 1 81284-831 INJECTION 0.40 mg INTRAVENOUS Unapproved drug for use in drug shortage 16 sections