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Identification
NamePhysostigmine
Accession NumberDB00981  (APRD00406)
TypeSmall Molecule
GroupsApproved
Description

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. [PubChem]

Structure
Thumb
Synonyms
Antilirium
Eserine
Physostigmine
Physostol
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Antilirium Inj 1mg/mlliquid1 mgintramuscular; intravenousForest Pharmaceuticals Inc.1975-12-311998-07-07Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Physostigmine Salicylateinjection1 mg/mLintravenousAkorn2010-08-10Not applicableUs
Physostigmine Salicylateinjection1 mg/mLintravenousCardinal Health2010-08-10Not applicableUs
International Brands
NameCompany
AntiliriumNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Physostigmine salicylate
ThumbNot applicableDBSALT001541
Physostigmine Sulfate
Thumb
  • InChI Key: YYBNDIVPHIWTPK-KYJQVDHRSA-N
  • Monoisotopic Mass: 648.294133104
  • Average Mass: 648.771
DBSALT000243
Categories
UNII9U1VM840SP
CAS number57-47-6
WeightAverage: 275.3461
Monoisotopic: 275.163376931
Chemical FormulaC15H21N3O2
InChI KeyInChIKey=PIJVFDBKTWXHHD-HIFRSBDPSA-N
InChI
InChI=1S/C15H21N3O2/c1-15-7-8-17(3)13(15)18(4)12-6-5-10(9-11(12)15)20-14(19)16-2/h5-6,9,13H,7-8H2,1-4H3,(H,16,19)/t13-,15+/m1/s1
IUPAC Name
(3aS,8aR)-1,3a,8-trimethyl-1H,2H,3H,3aH,8H,8aH-pyrrolo[2,3-b]indol-5-yl N-methylcarbamate
SMILES
[H][C@]12N(C)CC[C@@]1(C)C1=C(C=CC(OC(=O)NC)=C1)N2C
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as pyrroloindoles. These are compounds containing a pyrroloindole moiety, which is a tricyclic heterocycle which consists of a pyrrole ring fused to an indole. Pyrrole is 5-membered ring consisting of four carbon atoms and one nitrogen atom. Indole is a bicyclic compound consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassPyrroloindoles
Direct ParentPyrroloindoles
Alternative Parents
Substituents
  • Pyrroloindole
  • Indole
  • Dialkylarylamine
  • Benzenoid
  • N-alkylpyrrolidine
  • Pyrrolidine
  • Pyrrole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of glaucoma, and in the treatment of severe anticholinergic toxicity.
PharmacodynamicsPhysostigmine is a parasympathomimetic, specifically, a reversible cholinesterase inhibitor which effectively increases the concentration of acetylcholine at the sites of cholinergic transmission. Physostigmine is used to treat glaucoma. Because it crosses the blood-brain barrier, it is also used to treat the central nervous system effects of atropine overdose and other anticholinergic drug overdoses. Physostigmine can reverse both central and peripheral anticholinergia.
Mechanism of actionPhysostigmine inhibits acetylcholinesterase, the enzyme responsible for the breakdown of used acetylcholine. By interfering with the metabolism of acetylcholine, physostigmine indirectly stimulates both nicotinic and muscarinic receptors due to the consequential increase in available acetylcholine at the synapse.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Quickly hydrolyzed by cholinesterases

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicitySide effects include increased sweating, loss of bladder control, muscle weakness, nausea, vomiting, diarrhea, or stomach cramps or pain, shortness of breath, tightness in chest, or wheezing, slow or irregular heartbeat, unusual tiredness or weakness, watering of mouth, blurred vision or change in near or distant vision, and eye pain.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9975
Caco-2 permeable+0.5804
P-glycoprotein substrateSubstrate0.6631
P-glycoprotein inhibitor INon-inhibitor0.5442
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.7046
CYP450 2C9 substrateNon-substrate0.7838
CYP450 2D6 substrateNon-substrate0.6455
CYP450 3A4 substrateSubstrate0.7321
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8681
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9232
BiodegradationNot ready biodegradable0.8652
Rat acute toxicity4.7557 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9066
hERG inhibition (predictor II)Non-inhibitor0.8397
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Liquidintramuscular; intravenous1 mg
Injectionintravenous1 mg/mL
Prices
Unit descriptionCostUnit
Physostigmine salicyl cryst39.48USD g
Physostigmine 1 mg/ml ampul2.43USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point105.5 °CPhysProp
water solubility7760 mg/LNot Available
logP1.58HANSCH,C ET AL. (1995)
pKa6.12MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility0.992 mg/mLALOGPS
logP1.8ALOGPS
logP2.23ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)14.77ChemAxon
pKa (Strongest Basic)6.59ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area44.81 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity78.4 m3·mol-1ChemAxon
Polarizability30.62 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (9.24 KB)
SpectraNot Available
References
Synthesis Reference

Edward J. Glamkowski, Barbara E. Kurys, “4- and 6-carbamates related to physostigmine and intermediates for the preparation thereof.” U.S. Patent US5081117, issued September, 1978.

US5081117
General ReferencesNot Available
External Links
ATC CodesS01EB05V03AB19
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSDownload (73.3 KB)
Interactions
Drug Interactions
Drug
AcetylcholineThe risk or severity of adverse effects can be increased when Physostigmine is combined with Acetylcholine.
Atracurium besylatePhysostigmine may decrease the neuromuscular blocking activities of Atracurium besylate.
CarbacholThe risk or severity of adverse effects can be increased when Physostigmine is combined with Carbachol.
DipyridamoleThe therapeutic efficacy of Physostigmine can be decreased when used in combination with Dipyridamole.
FludrocortisoneThe risk or severity of adverse effects can be increased when Fludrocortisone is combined with Physostigmine.
NadololPhysostigmine may increase the bradycardic activities of Nadolol.
ProcyclidineThe therapeutic efficacy of Procyclidine can be decreased when used in combination with Physostigmine.
SuccinylcholineThe serum concentration of Succinylcholine can be increased when it is combined with Physostigmine.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Serine hydrolase activity
Specific Function:
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name:
ACHE
Uniprot ID:
P22303
Molecular Weight:
67795.525 Da
References
  1. Nguyen PV, Aniksztejn L, Catarsi S, Drapeau P: Maturation of neuromuscular transmission during early development in zebrafish. J Neurophysiol. 1999 Jun;81(6):2852-61. [PubMed:10368402 ]
  2. Tuovinen K, Kaliste-Korhonen E, Raushel FM, Hanninen O: Success of pyridostigmine, physostigmine, eptastigmine and phosphotriesterase treatments in acute sarin intoxication. Toxicology. 1999 Jun 15;134(2-3):169-78. [PubMed:10403635 ]
  3. Blasina MF, Faria AC, Gardino PF, Hokoc JN, Almeida OM, de Mello FG, Arruti C, Dajas F: Evidence for a noncholinergic function of acetylcholinesterase during development of chicken retina as shown by fasciculin. Cell Tissue Res. 2000 Feb;299(2):173-84. [PubMed:10741458 ]
  4. Monnet-Tschudi F, Zurich MG, Schilter B, Costa LG, Honegger P: Maturation-dependent effects of chlorpyrifos and parathion and their oxygen analogs on acetylcholinesterase and neuronal and glial markers in aggregating brain cell cultures. Toxicol Appl Pharmacol. 2000 Jun 15;165(3):175-83. [PubMed:10873710 ]
  5. Bolognesi ML, Andrisano V, Bartolini M, Minarini A, Rosini M, Tumiatti V, Melchiorre C: Hexahydrochromeno[4,3-b]pyrrole derivatives as acetylcholinesterase inhibitors. J Med Chem. 2001 Jan 4;44(1):105-9. [PubMed:11141093 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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Drug created on June 13, 2005 07:24 / Updated on December 03, 2015 09:51