You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NamePilocarpine
Accession NumberDB01085  (APRD00382)
Typesmall molecule
Groupsapproved
Description

A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. [PubChem]

Structure
Thumb
SynonymsNot Available
Salts
Name/CAS Structure Properties
Pilocarpine Hydrochloride
Thumb
  • InChI Key: RNAICSBVACLLGM-GNAZCLTHSA-N
  • Monoisotopic Mass: 244.097855505
  • Average Mass: 244.718
DBSALT000307
Brand names
NameCompany
DiocarpineNot Available
MiocarpineNot Available
PilostatNot Available
PiloviscNot Available
SalagenNot Available
TimpiloNot Available
Brand mixtures
Brand NameIngredients
E-Pilo 1 Ophthalmic SolutionEpinephrine bitartrate + Pilocarpine hydrochloride
E-Pilo 2 Ophthalmic SolutionEpinephrine bitartrate + Pilocarpine hydrochloride
E-Pilo 4 Ophthalmic SolutionEpinephrine Bitartrate + Pilocarpine Hydrochloride
E-Pilo 6 Ophthalmic SolutionEpinephrine Bitartrate + Pilocarpine Hydrochloride
E-Pilo-1 Oph SolnEpinephrine Bitartrate + Pilocarpine Hydrochloride
E-Pilo-2 Oph SolnEpinephrine Bitartrate + Pilocarpine Hydrochloride
E-Pilo-4 Oph SolnEpinephrine Bitartrate + Pilocarpine Hydrochloride
E-Pilo-6 Oph SolnEpinephrine Bitartrate + Pilocarpine Hydrochloride
Timpilo 2Pilocarpine Hydrochloride + Timolol Maleate
Timpilo 4Pilocarpine Hydrochloride + Timolol Maleate
Categories
CAS number54-71-7
WeightAverage: 208.2569
Monoisotopic: 208.121177766
Chemical FormulaC11H16N2O2
InChI KeyQCHFTSOMWOSFHM-WPRPVWTQSA-N
InChI
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
IUPAC Name
(3S,4R)-3-ethyl-4-[(1-methyl-1H-imidazol-5-yl)methyl]oxolan-2-one
SMILES
CC[C@H]1[C@@H](CC2=CN=CN2C)COC1=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassAlkaloids and Derivatives
ClassNot Available
SubclassNot Available
Direct parentAlkaloids and Derivatives
Alternative parentsN-substituted Imidazoles; Tetrahydrofurans; Oxolanes; Carboxylic Acid Esters; Lactones; Polyamines
Substituentsn-substituted imidazole; gamma butyrolactone; oxolane; imidazole; tetrahydrofuran; azole; carboxylic acid ester; lactone; polyamine; carboxylic acid derivative; organonitrogen compound; amine
Classification descriptionThis compound belongs to the 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.
Pharmacology
IndicationFor the treatment of radiation-induced dry mouth (xerostomia) and symptoms of dry mouth in patients with Sjögrens syndrome.
PharmacodynamicsPilocarpine is a choline ester miotic and a positively charged quaternary ammonium compound. Pilocarpine, in appropriate dosage, can increase secretion by the exocrine glands. The sweat, salivary, lacrimal, gastric, pancreatic, and intestinal glands and the mucous cells of the respiratory tract may be stimulated. When applied topically to the eye as a single dose it causes miosis, spasm of accommodation, and may cause a transitory rise in intraocular pressure followed by a more persistent fall. Dose-related smooth muscle stimulation of the intestinal tract may cause increased tone, increased motility, spasm, and tenesmus. Bronchial smooth muscle tone may increase. The tone and motility of urinary tract, gallbladder, and biliary duct smooth muscle may be enhanced. Pilocarpine may have paradoxical effects on the cardiovascular system. The expected effect of a muscarinic agonist is vasodepression, but administration of pilocarpine may produce hypertension after a brief episode of hypotension. Bradycardia and tachycardia have both been reported with use of pilocarpine.
Mechanism of actionPilocarpine 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.
AbsorptionThere 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
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Possibly occurs at the neuronal synapses and in the plasma

Route of eliminationNot Available
Half life0.76 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9816
Blood Brain Barrier + 0.9758
Caco-2 permeable + 0.6202
P-glycoprotein substrate Non-substrate 0.5806
P-glycoprotein inhibitor I Non-inhibitor 0.8457
P-glycoprotein inhibitor II Non-inhibitor 0.9432
Renal organic cation transporter Non-inhibitor 0.6467
CYP450 2C9 substrate Non-substrate 0.8408
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.6665
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.8732
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Inhibitor 0.7961
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8682
Ames test Non AMES toxic 0.6957
Carcinogenicity Non-carcinogens 0.9166
Biodegradation Not ready biodegradable 0.6808
Rat acute toxicity 2.6826 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9432
hERG inhibition (predictor II) Non-inhibitor 0.9009
Pharmacoeconomics
Manufacturers
  • Akorn inc
  • Alcon laboratories inc
  • Alcon inc
  • Corepharma llc
  • Impax laboratories inc
  • Lannett holdings inc
  • Roxane laboratories inc
  • Eisai inc
Packagers
Dosage forms
FormRouteStrength
GelOphthalmic
LiquidOphthalmic
LiquidOral
SolutionOphthalmic
Solution / dropsOral
TabletOral
Prices
Unit descriptionCostUnit
Pilopine HS 4% Gel 4 gm Tube64.08USDtube
Isopto Carpine 4% Solution 15ml Bottle37.5USDbottle
Isopto Carpine 4% Solution 30ml Bottle36.99USDbottle
Isopto Carpine 1% Solution 15ml Bottle36.37USDbottle
Isopto Carpine 2% Solution 15ml Bottle36.36USDbottle
Pilocarpine HCl 2% Solution 15ml Bottle35.01USDbottle
Isopto Carpine 2% Solution 30ml Bottle34.99USDbottle
Pilocarpine HCl 1% Solution 15ml Bottle32.24USDbottle
Pilocar 6% Solution 15ml Bottle15.99USDbottle
Pilopine hs 4% eye gel15.24USDg
Pilocar 4% Solution 15ml Bottle14.99USDbottle
Pilocar 1% Solution 15ml Bottle13.99USDbottle
Pilocar 2% Solution 15ml Bottle13.99USDbottle
Pilocar 0.5% Solution 15ml Bottle12.99USDbottle
Pilocarpine nitrate crystal9.85USDg
Pilocarpine hcl crystals8.19USDg
Pilocarpine 1% eye drops2.88USDml
Pilocarpine 2% eye drops2.88USDml
Pilocarpine 4% eye drops2.88USDml
Pilopine Hs 4 % Gel2.81USDg
Salagen 7.5 mg tablet2.48USDtablet
Isopto carpine 4% eye drops2.37USDml
Isopto carpine 2% eye drops2.26USDml
Isopto carpine 1% eye drops2.21USDml
Salagen 5 mg tablet2.14USDtablet
Pilocarpine hcl 7.5 mg tablet1.99USDtablet
Pilocarpine hcl 5 mg tablet1.55USDtablet
Salagen 5 mg Tablet1.23USDtablet
Pilocarpine 6% eye drops0.87USDml
Piloptic-6 eye drops0.87USDml
Piloptic-3 eye drops0.71USDml
Pilocarpine 3% eye drops0.53USDml
Pilocarpine 0.5% eye drops0.43USDml
Isopto Carpine 4 % Solution0.3USDml
Isopto Carpine 2 % Solution0.27USDml
Isopto Carpine 1 % Solution0.23USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point204-205 °CPhysProp
water solubility1E+006 mg/L (at 25 °C)SEIDELL,A (1941)
logP1.1Not Available
pKa6.78Not Available
Predicted Properties
PropertyValueSource
water solubility2.07e+00 g/lALOGPS
logP1.15ALOGPS
logP0.95ChemAxon
logS-2ALOGPS
pKa (strongest basic)6.61ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count0ChemAxon
polar surface area44.12ChemAxon
rotatable bond count3ChemAxon
refractivity56.53ChemAxon
polarizability22.34ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
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.

US5059531
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00525
KEGG CompoundC07474
PubChem Compound5910
PubChem Substance46507475
ChemSpider5699
ChEBI39462
ChEMBLCHEMBL611494
Therapeutic Targets DatabaseDAP001113
PharmGKBPA450962
IUPHAR305
Guide to Pharmacology305
Drug Product Database2229556
RxListhttp://www.rxlist.com/cgi/generic3/salagen.htm
Drugs.comhttp://www.drugs.com/cdi/pilocarpine-drops.html
WikipediaPilocarpine
ATC CodesN07AX01S01EB01
AHFS Codes
  • 12:04.00
  • 52:20.00
  • 92:02.00*
PDB EntriesNot Available
FDA labelshow(160 KB)
MSDSshow(73.3 KB)
Interactions
Drug Interactions
Drug
TacrineThe acetylcholinesterase inhibitor, Tacrine, may increase the adverse/toxic effects of Pilocarpine, a cholinergic agonist. Monitor for increased cholinergic effects and toxicity.
Food InteractionsNot Available

Targets

1. Muscarinic acetylcholine receptor M3

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M3 P20309 Details

References:

  1. 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. Epub 2009 Jun 4. Pubmed
  2. 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. Epub 2008 Sep 29. Pubmed

2. Muscarinic acetylcholine receptor M1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M1 P11229 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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. Pubmed
  3. 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. Epub 2008 Sep 29. Pubmed

3. Muscarinic acetylcholine receptor M2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M2 P08172 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Moreno-Vinasco L, Verbout NG, Fryer AD, Jacoby DB: Retinoic acid prevents virus-induced airway hyperreactivity and M2 receptor dysfunction via anti-inflammatory and antiviral effects. Am J Physiol Lung Cell Mol Physiol. 2009 Aug;297(2):L340-6. Epub 2009 May 22. Pubmed
  3. 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. Epub 2008 Sep 29. Pubmed

Enzymes

1. Cytochrome P450 2A6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2A6 P11509 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13