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Identification
Name Misoprostol
Accession Number DB00929 (APRD00037)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Misoprostolum [INN-Latin]
Salts Not Available
Brand names
Name Company
Arthrotec
Cytotec
Brand mixtures Not Available
Categories
  • Anti-Ulcer Agents
  • Oxytocics
  • Abortifacient Agents, Nonsteroidal
  • Abortifacient Agents
  • Prostaglandins
CAS number 59122-46-2
Weight Average: 382.5341
Monoisotopic: 382.271924326
Chemical Formula C22H38O5
InChI Key InChIKey=OJLOPKGSLYJEMD-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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Prostaglandins
Substructures
  • Carboxylic Acids and Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Acetates
  • Ethers
  • Alcohols and Polyols
  • Ketones
  • Prostaglandins
Pharmacology
Indication Indicated 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.
Pharmacodynamics Misoprostol 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 action Misoprostol 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.
Absorption Misoprostol is extensively absorbed.
Volume of distribution Not Available
Protein binding 85%
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 elimination After a single oral dose of misoprostol to nursing mothers, misoprostol acid was excreted in breast milk.
Half life 20-40 minutes
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Gd searle llc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Misoprostol hpmc powder 152.0 USD g
Cytotec 60 200 mcg tablet Bottle 121.93 USD bottle
Cytotec 60 100 mcg tablet Bottle 81.36 USD bottle
Arthrotec 75 tablet ec 4.07 USD tablet
Arthrotec ec 50 mg-200 mcg tablet 2.99 USD tablet
Arthrotec ec 75 mg-200 mcg tablet 2.99 USD tablet
Arthrotec ec 75 tablet 2.96 USD tablet
Arthrotec 75 75-200 mg-mcg tablet 2.82 USD tablet
Arthrotec 50 50-200 mg-mcg tablet 2.7 USD tablet
Cytotec 200 mcg tablet 1.95 USD tablet
Cytotec 100 mcg tablet 1.34 USD tablet
Misoprostol 200 mcg tablet 1.22 USD tablet
Misoprostol 100 mcg tablet 0.84 USD tablet
Apo-Misoprostol 200 mcg Tablet 0.45 USD tablet
Apo-Misoprostol 100 mcg Tablet 0.27 USD tablet
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Patents
Country Patent Number Approved Expires (estimated)
United States 5601843 1994-02-11 2014-02-11
United States 5698225 1993-05-03 2010-05-03
Properties
State liquid
Experimental Properties
Property Value Source
water solubility >1.6 mg/mL at 25.0 °C Not Available
logP 3.6 Not Available
Predicted Properties
Property Value Source
water solubility 1.64e-02 g/l ALOGPS
logP 3.88 ALOGPS
logP 3.86 ChemAxon
logS -4.4 ALOGPS
pKa (strongest acidic) 14.68 ChemAxon
pKa (strongest basic) -0.95 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 83.83 ChemAxon
rotatable bond count 14 ChemAxon
refractivity 107.88 ChemAxon
polarizability 45.38 ChemAxon
References
Synthesis Reference Not Available
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
Resource Link
KEGG Drug D00419 Link_out
PubChem Compound 5282381 Link_out
PubChem Substance 46505041 Link_out
ChemSpider 4445541 Link_out
Therapeutic Targets Database DAP000358 Link_out
PharmGKB PA450523 Link_out
Drug Product Database 2248846 Link_out
RxList http://www.rxlist.com/cgi/generic/misopro.htm Link_out
Drugs.com http://www.drugs.com/cdi/misoprostol.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Misoprostol Link_out
ATC Codes
  • A02BB01
AHFS Codes
  • 56:28.28
PDB Entries Not Available
FDA label show (246 KB)
MSDS show (147 KB)
Interactions
Drug Interactions
Drug Interaction
Carbetocin Misoprostol 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

Pharmacological action: yes
Actions: agonist

Receptor for prostaglandin E2 (PGE2); the EP3 receptor may be involved in inhibition of gastric acid secretion, modulation of neurotransmitter release in central and peripheral neurons, inhibition of sodium and water reabsorption in kidney tubulus and contraction in uterine smooth muscle. The activity of this receptor can couple to both the inhibition of adenylate cyclase mediated by G-I proteins, and to an elevation of intracellular calcium. The various isoforms have identical ligand binding properties but can interact with different second messenger systems (By similarity)

Organism class: human
UniProt ID: P43115 Link_out
Gene: PTGER3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: agonist

Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. The subsequent raise in intracellular cAMP is responsible for the relaxing effect of this receptor on smooth muscle

Organism class: human
UniProt ID: P43116 Link_out
Gene: PTGER2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: agonist

Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics, intestinal epithelial transport, adrenal aldosterone secretion, and uterine function

Organism class: human
UniProt ID: P35408 Link_out
Gene: PTGER4
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19