T3DB: Pilocarpine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (4)XML

Targets (4)

Record Information

Version

2.0

Creation Date

2009-07-21 20:28:20 UTC

Update Date

2014-12-24 20:25:54 UTC

Accession Number

T3D2979

Identification

Common Name

Pilocarpine

Class

Small Molecule

Description

Pilocarpine is only found in individuals that have used or taken this drug. It is a slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. [PubChem]Pilocarpine is a cholinergic parasympathomimetic agent. It increase secretion by the exocrine glands, and produces contraction of the iris sphincter muscle and ciliary muscle (when given topically to the eyes) by mainly stimulating muscarinic receptors.

Compound Type

Cholinergic Agent
Drug
Ester
Ether
Metabolite
Miotic
Muscarinic Agonist
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(3S,4R)-3-Ethyldihydro-4-((1-methyl-1H-imidazol-5-yl)methyl)-2(3H)-furanone
(3S-cis)-3-Ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)methyl]-2(3H)-furanone
Adsorbocarpine
beta-Pilocarpine hydrochloride
Diocarpine
Miocarpine
Pilocarpin
Pilocarpine chloride
Pilocarpine HCl
Pilocarpine hydrochloride
Pilocarpine monohydrochloride
Pilocarpine muriate
Pilokarpin
Pilokarpin monohydrochloride
Pilostat
Pilovisc
Salagen
Spersacarpine
Spersacarpine hydrochloride
Timpilo

Chemical Formula

C₁₁H₁₆N₂O₂

Average Molecular Mass

208.257 g/mol

Monoisotopic Mass

208.121 g/mol

CAS Registry Number

54-71-7

IUPAC Name

(3S,4R)-3-ethyl-4-[(1-methyl-1H-imidazol-5-yl)methyl]oxolan-2-one

Traditional Name

pilocarpine

SMILES

[H][C@]1(CC2=CN=CN2C)COC(=O)[C@@]1([H])CC

InChI Identifier

InChI=1S/C11H16N2O2/c1-3-10-8(6-15-11(10)14)4-9-5-12-7-13(9)2/h5,7-8,10H,3-4,6H2,1-2H3/t8-,10-/m0/s1

InChI Key

InChIKey=QCHFTSOMWOSFHM-WPRPVWTQSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as alkaloids and derivatives. These are naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and more rarely other elements such as chlorine, bromine, and phosphorus.

Kingdom

Organic compounds

Super Class

Alkaloids and derivatives

Class

Not Available

Sub Class

Not Available

Direct Parent

Alkaloids and derivatives

Alternative Parents

Substituents

Alkaloid or derivatives
Gamma butyrolactone
N-substituted imidazole
Azole
Imidazole
Heteroaromatic compound
Tetrahydrofuran
Carboxylic acid ester
Lactone
Carboxylic acid derivative
Monocarboxylic acid or derivatives
Oxacycle
Azacycle
Organoheterocyclic compound
Organic nitrogen compound
Hydrocarbon derivative
Organic oxide
Organopnictogen compound
Carbonyl group
Organonitrogen compound
Organooxygen compound
Organic oxygen compound
Aromatic heteromonocyclic compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

pilocarpine (CHEBI:8207 )
Imidazole alkaloids (C07474 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	204-205°C
Boiling Point	Not Available
Solubility	1E+006 mg/L (at 25°C)
LogP	1.1

Predicted Properties

Property	Value	Source
Water Solubility	2.07 g/L	ALOGPS
logP	1.15	ALOGPS
logP	0.95	ChemAxon
logS	-2	ALOGPS
pKa (Strongest Basic)	6.61	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	44.12 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	56.53 m³·mol⁻¹	ChemAxon
Polarizability	22.34 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0006-9500000000-dadfea39cdf9ef51bb38	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 6V, Positive	splash10-0a4i-1090000000-2fd25e6044f26134a0aa	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-0002-9400000000-20a06057a274f78a95cd	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-0090000000-defeea6e1be7da5df19c	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-0002-9000000000-cb6dd4c8fd9faf642a5b	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 50V, Positive	splash10-0002-9100000000-a58d77d501ea8e44d237	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-1090000000-90bbfd0f103bf2df2350	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-0a4j-5290000000-d69679a4b81e0442184f	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 6V, Positive	splash10-0a4i-1190000000-b781ed76499fdad467c3	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-1090000000-a96142a7f969311e7a5b	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Positive	splash10-0a4j-7790000000-914d8ed86ae8535d11fa	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 6V, Positive	splash10-0002-9300000000-ad4d9d6aa3e5e27b8fc3	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-0090000000-2df89b2b774b30adf514	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-0090000000-bb2a8fea255c0847828f	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-0002-9300000000-3efb8b2920ff65a813d0	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-052b-9580000000-49f5b565991796fac6e9	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-0090000000-6baeabdd0794d63b5d1d	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 50V, Positive	splash10-0002-9100000000-2a0733ac2670b486cead	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-1190000000-7cb82eee0859eb856641	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 50V, Positive	splash10-0002-9100000000-9d497ccde6e92e5082ac	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-0690000000-786fb6f080bd545dbc39	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0cka-1920000000-56d387d24bcc6e2e3637	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9300000000-e57c52a1b125f83b1903	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-0190000000-fc43dc1afe8440f3e607	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0bt9-1930000000-b7fcb5510042754cd666	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a4j-9800000000-0f44a4b4787f9e119567	2016-08-03	View Spectrum

Toxicity Profile

Route of Exposure

Oral ; eye contact. There was a decrease in the rate of absorption of pilocarpine from SALAGEN Tablets when taken with a high fat meal by 12 healthy male volunteers

Mechanism of Toxicity

Pilocarpine is a cholinergic parasympathomimetic agent. It increase secretion by the exocrine glands, and produces contraction of the iris sphincter muscle and ciliary muscle (when given topically to the eyes) by mainly stimulating muscarinic receptors.

Metabolism

Possibly occurs at the neuronal synapses and in the plasma Half Life: 0.76 hours

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For the treatment of radiation-induced dry mouth (xerostomia) and symptoms of dry mouth in patients with Sjögrens syndrome.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Overdosage should be treated with atropine titration (0. 5 mg to 1. 0 mg given subcutaneously or intravenously) and supportive measures to maintain respiration and circulation. Epinephrine (0. 3 mg to 1. 0 mg, subcutaneously or intramuscularly) may also be of value in the presence of severe cardiovascular depression or bronchoconstriction. (2)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

39462

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Pilocarpine

PDB ID

9PL

ACToR ID

Not Available

Wikipedia Link

Pilocarpine

References

Synthesis Reference

Gerhard R. Reuther, “Process for the preparation of pilocarpine from in vitro cultures of pilocarpus.” U.S. Patent US5059531, issued June, 1987.

MSDS

Link

General References

Drugs.com [Link]
RxList: The Internet Drug Index (2009). [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Muscarinic acetylcholine receptor M1

General Function:: Phosphatidylinositol phospholipase c activity
Specific Function:: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:: CHRM1
Uniprot ID:: P11229
Molecular Weight:: 51420.375 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.012 uM	Not Available	BindingDB 50008072

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Mei L, Lai J, Yamamura HI, Roeske WR: Pharmacologic comparison of selected agonists for the M1 muscarinic receptor in transfected murine fibroblast cells (B82). J Pharmacol Exp Ther. 1991 Feb;256(2):689-94. [1704434 ]
Jakubik J, Bacakova L, El-Fakahany EE, Tucek S: Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors. Mol Pharmacol. 1997 Jul;52(1):172-9. [9224827 ]

Target Details

2. Muscarinic acetylcholine receptor M3

General Function:: Receptor activity
Specific Function:: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:: CHRM3
Uniprot ID:: P20309
Molecular Weight:: 66127.445 Da

References

Sykes DA, Dowling MR, Charlton SJ: Exploring the mechanism of agonist efficacy: a relationship between efficacy and agonist dissociation rate at the muscarinic M3 receptor. Mol Pharmacol. 2009 Sep;76(3):543-51. doi: 10.1124/mol.108.054452. Epub 2009 Jun 4. [19498041 ]
Figueroa KW, Griffin MT, Ehlert FJ: Selectivity of agonists for the active state of M1 to M4 muscarinic receptor subtypes. J Pharmacol Exp Ther. 2009 Jan;328(1):331-42. doi: 10.1124/jpet.108.145219. Epub 2008 Sep 29. [18824613 ]
Jakubik J, Bacakova L, El-Fakahany EE, Tucek S: Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors. Mol Pharmacol. 1997 Jul;52(1):172-9. [9224827 ]

Target Details

3. Muscarinic acetylcholine receptor M2

General Function:: G-protein coupled acetylcholine receptor activity
Specific Function:: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
Gene Name:: CHRM2
Uniprot ID:: P08172
Molecular Weight:: 51714.605 Da

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Jakubik J, Bacakova L, El-Fakahany EE, Tucek S: Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors. Mol Pharmacol. 1997 Jul;52(1):172-9. [9224827 ]

Target Details

4. Muscarinic acetylcholine receptor M4

General Function:: Guanyl-nucleotide exchange factor activity
Specific Function:: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
Gene Name:: CHRM4
Uniprot ID:: P08173
Molecular Weight:: 53048.65 Da

References

Jakubik J, Bacakova L, El-Fakahany EE, Tucek S: Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors. Mol Pharmacol. 1997 Jul;52(1):172-9. [9224827 ]

Pilocarpine (T3D2979)

Structure for T3D2979: Pilocarpine

Targets

Binding/Activity Constants

References

References

References

References