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Identification
NameMisoprostol
Accession NumberDB00929  (APRD00037)
Typesmall molecule
Groupsapproved
Description

A synthetic analog of natural prostaglandin E1. It produces a dose-related inhibition of gastric acid and pepsin secretion, and enhances mucosal resistance to injury. It is an effective anti-ulcer agent and also has oxytocic properties. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
CytotecNot AvailableNot Available
MisoprostolumLatinINN
SaltsNot Available
Brand names
NameCompany
ArthrotecNot Available
CytotecNot Available
Brand mixturesNot Available
Categories
CAS number59122-46-2
WeightAverage: 382.5341
Monoisotopic: 382.271924326
Chemical FormulaC22H38O5
InChI KeyOJLOPKGSLYJEMD-URPKTTJQSA-N
InChI
InChI=1S/C22H38O5/c1-4-5-14-22(2,26)15-10-12-18-17(19(23)16-20(18)24)11-8-6-7-9-13-21(25)27-3/h10,12,17-18,20,24,26H,4-9,11,13-16H2,1-3H3/b12-10+/t17-,18-,20-,22?/m1/s1
IUPAC Name
methyl 7-[(1R,2R,3R)-3-hydroxy-2-[(1E)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate
SMILES
CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassEicosanoids
SubclassProstaglandins and related compounds
Direct parentProstaglandins and related compounds
Alternative parentsFatty Acid Esters; Tertiary Alcohols; Carboxylic Acid Esters; Ketones; Secondary Alcohols; Cyclic Alcohols and Derivatives; Ethers; Enolates; Polyamines
Substituentsfatty acid ester; tertiary alcohol; cyclic alcohol; secondary alcohol; ketone; carboxylic acid ester; carboxylic acid derivative; ether; enolate; polyamine; alcohol; carbonyl group
Classification descriptionThis compound belongs to the prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid.
Pharmacology
IndicationIndicated for the treatment of ulceration (duodenal, gastric and NSAID induced) and prophylaxis for NSAID induced ulceration. Misoprostol is also indicated for other uses that are not approved in Canada, including the medical termination of an intrauterine pregnancy used alone or in combination with methotrexate,as well as the induction of labour in a selected population of pregnant women with unfavourable cervices. This indication is avoided in women with prior uterine surgery or cesarean surgery due to an increased risk of possible uterine rupture. Misoprostol is also used for the prevention or treatment of serious postpartum hemorrhage.
PharmacodynamicsMisoprostol is a prostaglandin E1 (PGE1) analogue used for the treatment and prevention of stomach ulcers. When administered, misoprostol stimulates increased secretion of the protective mucus that lines the gastrointestinal tract and increases mucosal blood flow, thereby increasing mucosal integrity. It is sometimes co-prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) to prevent the occurrence of gastric ulceration, a common adverse effect of the NSAIDs.
Mechanism of actionMisoprostol seems to inhibit gastric acid secretion by a direct action on the parietal cells through binding to the prostaglandin receptor. The activity of this receptor is mediated by G proteins which normally activate adenylate cyclase. The indirect inhibition of adenylate cyclase by Misoprostol may be dependent on guanosine-5’-triphosphate (GTP). The significant cytoprotective actions of misoprostol are related to several mechanisms. These include: 1. Increased secretion of bicarbonate, 2. Considerable decrease in the volume and pepsin content of the gastric secretions, 3. It prevents harmful agents from disrupting the tight junctions between the epithelial cells which stops the subsequent back diffusion of H+ ions into the gastric mucosa, 4. Increased thickness of mucus layer, 5. Enhanced mucosal blood flow as a result of direct vasodilatation, 6. Stabilization of tissue lysozymes/vascular endothelium, 7. Improvement of mucosal regeneration capacity, and 8. Replacement of prostaglandins that have been depleted as a result of various insults to the area. Misoprostol has also been shown to increase the amplitude and frequency of uterine contractions during pregnancy via selective binding to the EP-2/EP-3 prostanoid receptors.
AbsorptionMisoprostol is extensively absorbed.
Volume of distributionNot Available
Protein binding85%
Metabolism

Rapidly de-esterified to misoprostol acid. The de-esterified metabolite undergoes further metabolism by beta and omega oxidation; oxidation is followed by reduction of the ketone to yield prostaglandin F analogs.

Route of eliminationAfter a single oral dose of misoprostol to nursing mothers, misoprostol acid was excreted in breast milk.
Half life20-40 minutes
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 + 0.9157
Blood Brain Barrier + 0.938
Caco-2 permeable - 0.5339
P-glycoprotein substrate Substrate 0.6607
P-glycoprotein inhibitor I Non-inhibitor 0.7261
P-glycoprotein inhibitor II Inhibitor 0.6504
Renal organic cation transporter Non-inhibitor 0.9146
CYP450 2C9 substrate Non-substrate 0.857
CYP450 2D6 substrate Non-substrate 0.9024
CYP450 3A4 substrate Substrate 0.6281
CYP450 1A2 substrate Non-inhibitor 0.8358
CYP450 2C9 substrate Non-inhibitor 0.8175
CYP450 2D6 substrate Non-inhibitor 0.9459
CYP450 2C19 substrate Non-inhibitor 0.8199
CYP450 3A4 substrate Non-inhibitor 0.795
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9591
Ames test Non AMES toxic 0.8289
Carcinogenicity Non-carcinogens 0.8941
Biodegradation Not ready biodegradable 0.8797
Rat acute toxicity 3.7051 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.964
hERG inhibition (predictor II) Non-inhibitor 0.8734
Pharmacoeconomics
Manufacturers
  • Gd searle llc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Misoprostol hpmc powder152.0USDg
Cytotec 60 200 mcg tablet Bottle121.93USDbottle
Cytotec 60 100 mcg tablet Bottle81.36USDbottle
Arthrotec 75 tablet ec4.07USDtablet
Arthrotec ec 50 mg-200 mcg tablet2.99USDtablet
Arthrotec ec 75 mg-200 mcg tablet2.99USDtablet
Arthrotec ec 75 tablet2.96USDtablet
Arthrotec 75 75-200 mg-mcg tablet2.82USDtablet
Arthrotec 50 50-200 mg-mcg tablet2.7USDtablet
Cytotec 200 mcg tablet1.95USDtablet
Cytotec 100 mcg tablet1.34USDtablet
Misoprostol 200 mcg tablet1.22USDtablet
Misoprostol 100 mcg tablet0.84USDtablet
Apo-Misoprostol 200 mcg Tablet0.45USDtablet
Apo-Misoprostol 100 mcg Tablet0.27USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States56018431994-02-112014-02-11
United States56982251993-05-032010-05-03
Properties
Stateliquid
Experimental Properties
PropertyValueSource
water solubility>1.6 mg/mL at 25.0 °CNot Available
logP3.6Not Available
Predicted Properties
PropertyValueSource
water solubility1.64e-02 g/lALOGPS
logP3.88ALOGPS
logP3.86ChemAxon
logS-4.4ALOGPS
pKa (strongest acidic)14.68ChemAxon
pKa (strongest basic)-0.95ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count2ChemAxon
polar surface area83.83ChemAxon
rotatable bond count14ChemAxon
refractivity107.88ChemAxon
polarizability45.38ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Salah Ahmed, Raj Mahajan, “Vaginal tablets comprising misoprostol and methods of making and using the same.” U.S. Patent US20070071814, issued March 29, 2007.

US20070071814
General Reference
  1. Costa SH, Vessey MP: Misoprostol and illegal abortion in Rio de Janeiro, Brazil. Lancet. 1993 May 15;341(8855):1258-61. Pubmed
  2. Coelho HL, Teixeira AC, Cruz Mde F, Gonzaga SL, Arrais PS, Luchini L, La Vecchia C, Tognoni G: Misoprostol: the experience of women in Fortaleza, Brazil. Contraception. 1994 Feb;49(2):101-10. Pubmed
  3. Barbosa RM, Arilha M: The Brazilian experience with Cytotec. Stud Fam Plann. 1993 Jul-Aug;24(4):236-40. Pubmed
  4. Rocha J: Brazil investigates drug’s possible link with birth defects. BMJ. 1994 Sep 24;309(6957):757-8. Pubmed
  5. Gonzalez CH, Vargas FR, Perez AB, Kim CA, Brunoni D, Marques-Dias MJ, Leone CR, Correa Neto J, Llerena Junior JC, de Almeida JC: Limb deficiency with or without Mobius sequence in seven Brazilian children associated with misoprostol use in the first trimester of pregnancy. Am J Med Genet. 1993 Aug 1;47(1):59-64. Pubmed
External Links
ResourceLink
KEGG DrugD00419
PubChem Compound5282381
PubChem Substance46505041
ChemSpider4445541
Therapeutic Targets DatabaseDAP000358
PharmGKBPA450523
Drug Product Database2248846
RxListhttp://www.rxlist.com/cgi/generic/misopro.htm
Drugs.comhttp://www.drugs.com/cdi/misoprostol.html
WikipediaMisoprostol
ATC CodesA02BB01
AHFS Codes
  • 56:28.28
PDB EntriesNot Available
FDA labelshow(246 KB)
MSDSshow(147 KB)
Interactions
Drug Interactions
Drug
CarbetocinMisoprostol may enhance the therapeutic effect of Carbetocin. Avoid the concomitant use of carbetocin and misoprostol. The oxytocic activity of carbetocin (oxytocin analogue) may be augmented by agents used to promote cervical ripening (eg, dinoprostone, misoprostol). Dinoprostone (vaginal insert) prescribing information recommends waiting at least 30 minute following its removal before initiating treatment with oxytocic agents. A similar approach might be anticipated with misoprostol use.
Food Interactions
  • Take with food to decrease the incidence of diarrhea.

Targets

1. Prostaglandin E2 receptor EP3 subtype

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Prostaglandin E2 receptor EP3 subtype P43115 Details

References:

  1. Nakae K, Hayashi F, Hayashi M, Yamamoto N, Iino T, Yoshikawa S, Gupta J: Functional role of prostacyclin receptor in rat dorsal root ganglion neurons. Neurosci Lett. 2005 Nov 18;388(3):132-7. Pubmed
  2. Li J, Liang X, Wang Q, Breyer RM, McCullough L, Andreasson K: Misoprostol, an anti-ulcer agent and PGE2 receptor agonist, protects against cerebral ischemia. Neurosci Lett. 2008 Jun 20;438(2):210-5. Epub 2008 Apr 20. Pubmed
  3. Guan Y, Stillman BA, Zhang Y, Schneider A, Saito O, Davis LS, Redha R, Breyer RM, Breyer MD: Cloning and expression of the rabbit prostaglandin EP2 receptor. BMC Pharmacol. 2002 Jun 27;2:14. Pubmed
  4. Kiriyama M, Ushikubi F, Kobayashi T, Hirata M, Sugimoto Y, Narumiya S: Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1997 Sep;122(2):217-24. Pubmed
  5. Nataraj C, Thomas DW, Tilley SL, Nguyen MT, Mannon R, Koller BH, Coffman TM: Receptors for prostaglandin E(2) that regulate cellular immune responses in the mouse. J Clin Invest. 2001 Oct;108(8):1229-35. Pubmed

2. Prostaglandin E2 receptor EP2 subtype

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Prostaglandin E2 receptor EP2 subtype P43116 Details

References:

  1. Nakae K, Hayashi F, Hayashi M, Yamamoto N, Iino T, Yoshikawa S, Gupta J: Functional role of prostacyclin receptor in rat dorsal root ganglion neurons. Neurosci Lett. 2005 Nov 18;388(3):132-7. Pubmed
  2. Li J, Liang X, Wang Q, Breyer RM, McCullough L, Andreasson K: Misoprostol, an anti-ulcer agent and PGE2 receptor agonist, protects against cerebral ischemia. Neurosci Lett. 2008 Jun 20;438(2):210-5. Epub 2008 Apr 20. Pubmed
  3. Guan Y, Stillman BA, Zhang Y, Schneider A, Saito O, Davis LS, Redha R, Breyer RM, Breyer MD: Cloning and expression of the rabbit prostaglandin EP2 receptor. BMC Pharmacol. 2002 Jun 27;2:14. Pubmed
  4. Kiriyama M, Ushikubi F, Kobayashi T, Hirata M, Sugimoto Y, Narumiya S: Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1997 Sep;122(2):217-24. Pubmed
  5. Nataraj C, Thomas DW, Tilley SL, Nguyen MT, Mannon R, Koller BH, Coffman TM: Receptors for prostaglandin E(2) that regulate cellular immune responses in the mouse. J Clin Invest. 2001 Oct;108(8):1229-35. Pubmed

3. Prostaglandin E2 receptor EP4 subtype

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Prostaglandin E2 receptor EP4 subtype P35408 Details

References:

  1. Nakae K, Hayashi F, Hayashi M, Yamamoto N, Iino T, Yoshikawa S, Gupta J: Functional role of prostacyclin receptor in rat dorsal root ganglion neurons. Neurosci Lett. 2005 Nov 18;388(3):132-7. Pubmed
  2. Li J, Liang X, Wang Q, Breyer RM, McCullough L, Andreasson K: Misoprostol, an anti-ulcer agent and PGE2 receptor agonist, protects against cerebral ischemia. Neurosci Lett. 2008 Jun 20;438(2):210-5. Epub 2008 Apr 20. Pubmed
  3. Guan Y, Stillman BA, Zhang Y, Schneider A, Saito O, Davis LS, Redha R, Breyer RM, Breyer MD: Cloning and expression of the rabbit prostaglandin EP2 receptor. BMC Pharmacol. 2002 Jun 27;2:14. Pubmed
  4. Kiriyama M, Ushikubi F, Kobayashi T, Hirata M, Sugimoto Y, Narumiya S: Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1997 Sep;122(2):217-24. Pubmed
  5. Nataraj C, Thomas DW, Tilley SL, Nguyen MT, Mannon R, Koller BH, Coffman TM: Receptors for prostaglandin E(2) that regulate cellular immune responses in the mouse. J Clin Invest. 2001 Oct;108(8):1229-35. Pubmed
  6. Crider JY, Xu SX, Sharif NA: Pharmacology of functional endogenous IP prostanoid receptors in NCB-20 cells: comparison with binding data from human platelets. Prostaglandins Leukot Essent Fatty Acids. 2001 Nov-Dec;65(5-6):253-8. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12