U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C15H21N3O2
Molecular Weight 275.3461
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Physostigmine

SMILES

[H][C@]12N(C)CC[C@@]1(C)C3=C(C=CC(OC(=O)NC)=C3)N2C

InChI

InChIKey=PIJVFDBKTWXHHD-HIFRSBDPSA-N
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

HIDE SMILES / InChI
Physostigmine (Phy) is one of the oldest drug isolated from Calabar beans and successfully used for the treatment of glaucoma in 1864. Since then, it has been widely employed for various therapeutic purposes. Recently, it has gained prominence because of its clinical trials in the treatment of Alzheimer's disease. Physostigmine was used to treat glaucoma. It can be applied topically to the conjunctiva. Phy is also considered to be a potent prophylactic antidote for organophosphate poisoning. It is a reversible cholinesterase (ChE) inhibitor and has a short duration of action. For the last 50 years, numerous authors have shown that pretreatment with Phy would rapidly improve the incapacitating effects of organophosphate intoxication in various animal species. Phy carbamylates to a portion of ChE enzyme and thus protects the enzyme from binding with organophosphate, which are irreversible ChE inhibitors. The carbamylated ChE enzyme decarbamylates to free the enzyme for normal functioning. The rates of decarbamylation of butyrylcholinesterase (BuChE) in plasma and ChE in brain and muscle are different and are related to the half-life of Phy in these tissues. In addition to ChE inhibition, Phy has a direct action on acetylcholine (ACh) receptor ionophore complex by interacting with the ACh-gated cation channels. A cholinesterase inhibitor that is rapidly absorbed through membranes. 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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Physostigmine salicylate in the treatment of tricyclic antidepressant overdosage.
1975 Mar 3
Donepezil hydrochloride: a treatment drug for Alzheimer's disease.
2001
Clinical and institutional aspects of antidote therapy in Russia.
2001
Action of tacrine on muscarinic receptors in rat intestinal smooth muscle.
2001 Apr
[Anticholinergic syndrome after postoperative dimenhydrinate administration].
2001 Dec
Stimulation of minor salivary glands by intraoral treatment with the cholinesterase inhibitor physostigmine in man.
2001 Dec
Acetylcholinesterase blockade does not account for the adverse cardiovascular effects of the antitumor drug irinotecan: a preclinical study.
2001 Dec 1
Functional relationship between subfornical organ cholinergic stimulation and cellular activation in the hypothalamus and AV3V region.
2001 Dec 20
Aldrin-induced locomotor activity: possible involvement of the central GABAergic-cholinergic-dopaminergic interaction.
2001 Jan-Feb
The effect of betahistine on vestibular habituation: comparison of rotatory and sway habituation training.
2001 Jul
Septal GABAergic and hippocampal cholinergic systems modulate anxiety in the plus-maze and shock-probe tests.
2001 Jul-Aug
[Sensory reactions of hippocampal neurons in rabbit during functional suppression of theta rythm- controlling structures].
2001 Mar-Apr
Concurrent quantification of tremor and depression of locomotor activity induced in rats by harmaline and physostigmine.
2001 Nov
Estradiol decreases the acetylcholine-elicited airway reactivity in ovariectomized rats through an increase in epithelial acetylcholinesterase activity.
2001 Nov 15
Involvement of cholinergic and glutamatergic functions in working memory impairment induced by interleukin-1beta in rats.
2001 Nov 2
Methyl analogues of the experimental Alzheimer drug phenserine: synthesis and structure/activity relationships for acetyl- and butyrylcholinesterase inhibitory action.
2001 Nov 22
Infusions of physostigmine into the hippocampus or the entorhinal cortex attenuate avoidance retention deficits produced by intra-septal infusions of the GABA agonist muscimol.
2001 Nov 30
Long-term changes in hippocampus and neocortex EEG spectra in response to pharmacological treatments affecting the cholinergic system.
2001 Nov-Dec
The esterase-like activity of serum albumin may be due to cholinesterase contamination.
2001 Oct
Opioid receptor regulation of muscarinic acetylcholine receptor-mediated synaptic responses in the hippocampus.
2001 Oct
Synthesis, hydrolysis kinetics and anti-platelet effects of isosorbide mononitrate derivatives of aspirin.
2001 Oct
Muscarinic versus nicotinic modulation of a visual task. a pet study using drug probes.
2001 Oct
The glutamate receptor agonist, AMPA, induces acetylcholine release in guinea pig cochlea; a microdialysis study.
2001 Oct 5
Memory improving actions of gabapentin in mice: possible involvement of central muscarinic cholinergic mechanism.
2001 Oct 5
The combined effects of pyridostigmine and chronic stress on brain cortical and blood acetylcholinesterase, corticosterone, prolactin and alternation performance in rats.
2001 Oct-Nov
Developmental neurotoxicity of chlorpyrifos modeled in vitro: comparative effects of metabolites and other cholinesterase inhibitors on DNA synthesis in PC12 and C6 cells.
2001 Sep
Physostigmine as treatment for severe CNS anticholinergic toxicity.
2001 Sep
The use of physostigmine in the management of gamma-hydroxybutyrate overdose.
2001 Sep
Use of physostigmine in the management of gamma-hydroxybutyrate overdose.
2001 Sep
The use of carbamates, atropine, and 2-pyridine aldoxime methoiodide in the protection of Artemia salina against poisoning by carbophenothion.
2001 Sep
Release of non-neuronal acetylcholine from the human placenta: difference to neuronal acetylcholine.
2001 Sep
Acetylcholine mediates the estrogen-induced increase in NMDA receptor binding in CA1 of the hippocampus and the associated improvement in working memory.
2001 Sep 1
Doxepin-induced torsade de pointes tachycardia.
2001 Sep 4
Reduction of cortical amyloid beta levels in guinea pig brain after systemic administration of physostigmine.
2001 Sep 7
Selective activity of butyrylcholinesterase in serum by a chemiluminescent assay.
2001 Sep-Oct
Eptastigmine: ten years of pharmacology, toxicology, pharmacokinetic, and clinical studies.
2001 Winter
Donepezil for Alzheimer's disease: pharmacodynamic, pharmacokinetic, and clinical profiles.
2001 Winter
Efficient formal total synthesis of physostigmine and physovenine: conformational analysis of key intermediates.
2002 Feb
Mechanism of vascular relaxation by cholinomimetic drugs with special reference to pilocarpine and arecoline.
2002 Feb
Physostigmine, sodium bicarbonate, or hypertonic saline to treat diphenhydramine toxicity.
2002 Feb
Heterogeneity of release-inhibiting muscarinic autoreceptors in heart atria and urinary bladder: a study with M(2)- and M(4)-receptor-deficient mice.
2002 Feb
Biochemical analysis of a native and proteolytic fragment of a high-molecular-weight thermostable lipase from a mesophilic Bacillus sp.
2002 Feb
Involvement of mu(1)-opioid receptors and cholinergic neurotransmission in the endomorphins-induced impairment of passive avoidance learning in mice.
2002 Feb 1
Pharmacological properties of nicotinic acetylcholine receptors in isolated Locusta migratoria neurones.
2002 Feb 15
Presynaptic modulation of cholinergic neurotransmission in the human proximal stomach.
2002 Jan
A novel class of peptides with facilitating action on neuronal nicotinic receptors of rat chromaffin cells in vitro: functional and molecular dynamics studies.
2002 Jan
In vitro effects of organophosphorus anticholinesterases on muscarinic receptor-mediated inhibition of acetylcholine release in rat striatum.
2002 Jan 15
Alternative splicing and neuritic mRNA translocation under long-term neuronal hypersensitivity.
2002 Jan 18
Central anticholinergics to treat nerve-agent poisoning.
2002 Jan 19
Physostigmine does not antagonize sevoflurane anesthesia assessed by bispectral index or enhances recovery.
2002 Mar
Patents

Sample Use Guides

For glaucoma: Adults and children—Use in each eye one to three times a day.
Route of Administration: Other
The increased number of BrdU- and proliferating cell nuclear antigen-labeled cells were shown in zebrafish treated with 200 μM physostigmine, which was inhibited by pretreatment with 200 μM scopolamine. iNOS mRNA expression was increased in the brain of zebrafish treated with 200 μM physostigmine. Consistently, aminoguanidine, an iNOS inhibitor, attenuated the increase in the number of BrdU-labeled cells by physostigmine treatment. Zebrafish also showed seizure-like locomotor activity characterized by a rapid and abrupt movement during a 30 min treatment with 200 μM physostigmine. Neural activity in response to an electrical stimulus was increased in the isolated telencephalon of zebrafish continuously perfused with 200 μM physostigmine.
Name Type Language
Physostigmine
HSDB   MART.   MI   USP   VANDF   WHO-DD  
Common Name English
PHYSOSTIGMINE [MI]
Common Name English
NSC-30782
Code English
ESERIN
Common Name English
PHYSOSTIGMINE [USP IMPURITY]
Common Name English
ESERINUM [HPUS]
Common Name English
PYRROLO(2,3-B)INDOL-5-OL, 1,2,3,3A,8,8A-HEXAHYDRO-1,3A,8-TRIMETHYL-, METHYLCARBAMATE (ESTER), (3AS-CIS)
Common Name English
Physostigmine [WHO-DD]
Common Name English
PHYSOSTIGMINE [HSDB]
Common Name English
1,2,3,3A.BETA.,8A.BETA.-HEXAHYDRO-1,3A,8-TRIMETHYLPYRROLO(2,3-B)-INDOL-5-YL METHYLCARBAMATE
Common Name English
MCV-4484
Code English
ESERINUM
HPUS  
Common Name English
(-)-PHYSOSTIGMINE
Common Name English
PHYSOSTIGMINE [VANDF]
Common Name English
PHYSOSTIGMINE [MART.]
Common Name English
COGMINE
Brand Name English
ESERINE
Common Name English
Classification Tree Code System Code
WHO-VATC QS01EB05
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
WHO-ATC S01EB05
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
NCI_THESAURUS C47792
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
WHO-VATC QA03FA90
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
WHO-VATC QA03AX90
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
WHO-VATC QV03AB19
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
LIVERTOX 776
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
WHO-ATC V03AB19
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
Code System Code Type Description
HSDB
3161
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
DAILYMED
9U1VM840SP
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
CHEBI
27953
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
SMS_ID
100000079444
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
FDA UNII
9U1VM840SP
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
EPA CompTox
DTXSID3023471
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
CAS
57-47-6
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
MESH
D010830
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
IUPHAR
6598
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
LACTMED
Physostigmine
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
DRUG CENTRAL
2159
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
ChEMBL
CHEMBL94
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
MERCK INDEX
m8766
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY Merck Index
PUBCHEM
5983
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
WIKIPEDIA
PHYSOSTIGMINE
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
NSC
30782
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
ECHA (EC/EINECS)
200-332-8
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
RXCUI
8299
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY RxNorm
DRUG BANK
DB00981
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
EVMPD
SUB14864MIG
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY
NCI_THESAURUS
C81337
Created by admin on Fri Dec 15 15:01:04 GMT 2023 , Edited by admin on Fri Dec 15 15:01:04 GMT 2023
PRIMARY