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

Details

Stereochemistry ABSOLUTE
Molecular Formula C15H21N3O2.C7H6O3
Molecular Weight 413.4669
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PHYSOSTIGMINE SALICYLATE

SMILES

OC(=O)C1=C(O)C=CC=C1.[H][C@]23N(C)CC[C@@]2(C)C4=C(C=CC(OC(=O)NC)=C4)N3C

InChI

InChIKey=HZOTZTANVBDFOF-PBCQUBLHSA-N
InChI=1S/C15H21N3O2.C7H6O3/c1-15-7-8-17(3)13(15)18(4)12-6-5-10(9-11(12)15)20-14(19)16-2;8-6-4-2-1-3-5(6)7(9)10/h5-6,9,13H,7-8H2,1-4H3,(H,16,19);1-4,8H,(H,9,10)/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
Synthesis of the signal molecule acetylcholine during the developmental cycle of Paramecium primaurelia (Protista, Ciliophora) and its possible function in conjugation.
2001 Jun
[Sensory reactions of hippocampal neurons in rabbit during functional suppression of theta rythm- controlling structures].
2001 Mar-Apr
Effects of right and left vagal stimulation on left ventricular acetylcholine levels in the cat.
2001 May
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
The combined effects of pyridostigmine and chronic stress on brain cortical and blood acetylcholinesterase, corticosterone, prolactin and alternation performance in rats.
2001 Oct-Nov
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 SALICYLATE
EP   JAN   MART.   MI   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
Common Name English
PHYSOSTIGMINI SALICYLAS [WHO-IP LATIN]
Common Name English
PHYSOSTIGMINE SALICYLATE [MI]
Common Name English
ANTILIRIUM
Brand Name English
PHYSOSTIGMINE SALICYLATE [WHO-IP]
Common Name English
PHYSOSTIGMINE SALICYLATE [VANDF]
Common Name English
PHYSOSTIGMINE SALICYLATE [MART.]
Common Name English
PHYSOSTIGMINE SALICYLATE [USP-RS]
Common Name English
ISOPTO ESERINE
Common Name English
NSC-757275
Code English
ESERINE SALICYLATE
Common Name English
Physostigmine monosalicylate
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)-, MONO(2-HYDROXYBENZOATE)
Common Name English
PHYSOSTIGMINE SALICYLATE [EP MONOGRAPH]
Common Name English
PHYSOSTIGMINE SALICYLATE [JAN]
Common Name English
PHYSOSTIGMINE SALICYLATE [USP MONOGRAPH]
Common Name English
Physostigmine salicylate [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C47792
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
FDA ORPHAN DRUG 183
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
Code System Code Type Description
CHEBI
27953
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
PRIMARY
DRUG BANK
DBSALT001541
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
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RS_ITEM_NUM
1537003
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
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ChEMBL
CHEMBL94
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
PRIMARY
DAILYMED
2046ZRO9VU
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
PRIMARY
CAS
57-64-7
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
PRIMARY
NSC
757275
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
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MESH
C026718
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
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ECHA (EC/EINECS)
200-343-8
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
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RXCUI
33656
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
PRIMARY RxNorm
EPA CompTox
DTXSID80883232
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MERCK INDEX
m8766
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
PRIMARY Merck Index
SMS_ID
100000079464
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
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NCI_THESAURUS
C81336
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
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FDA UNII
2046ZRO9VU
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
PHYSOSTIGMINE SALICYLATE
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
PRIMARY Description: Colourless crystals; odourless. Solubility: Sparingly soluble in water; soluble in ethanol (~750 g/l) TS; slightly soluble in ether R. Category: Anticholinesterase; miotic. Storage: Physostigmine salicylate should be kept in a tightly closed container, protected from light, and preferably in quantitiesnot exceeding 1 g. Additional information: Physostigmine salicylate is very poisonous. It acquires a red tint when exposed to air or light. All testsshould be performed on freshly prepared solutions. Definition: Physostigmine salicylate contains not less than 98.0% and not more than 101.0% of C15H21N3O2,C7H6O3, calculatedwith reference to the dried substance.
PUBCHEM
5992
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
PRIMARY
EVMPD
SUB14865MIG
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
PRIMARY
CHEBI
48883
Created by admin on Fri Dec 15 15:16:57 GMT 2023 , Edited by admin on Fri Dec 15 15:16:57 GMT 2023
PRIMARY