DT-Web

DB00929 - Misoprostol


Identification
Name Misoprostol
Accession Number DB00929 (APRD00037)
Type small molecule
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
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 382.5341
Groups approved
Monoisotopic Weight 382.271924326
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.
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.
Protein binding 85%
Biotransformation 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.
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of 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


Prostaglandin E2 receptor, EP3 subtype
Name Prostaglandin E2 receptor, EP3 subtype
Gene Name PTGER3
Pharmacological action yes
Actions agonist
References
  • 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
  • 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
  • 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
  • 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
  • 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
DTHybrid score 0.772
Prostaglandin E2 receptor, EP2 subtype
Name Prostaglandin E2 receptor, EP2 subtype
Gene Name PTGER2
Pharmacological action yes
Actions agonist
References
  • 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
  • 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
  • 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
  • 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
  • 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
DTHybrid score 0.7464
Prostaglandin E2 receptor EP4 subtype
Name Prostaglandin E2 receptor EP4 subtype
Gene Name PTGER4
Pharmacological action unknown
Actions agonist
References
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
DTHybrid score 0.7322

Predictions


Id Partner name Gene Name Score
73 Prostaglandin E2 receptor, EP1 subtype PTGER1 0.2005
672 Prostaglandin F2-alpha receptor PTGFR 0.0955
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.0906
6152 Solute carrier organic anion transporter family member 2A1 SLCO2A1 0.0807
6136 Multidrug resistance-associated protein 5 ABCC5 0.0751
650 Aldo-keto reductase family 1 member C3 AKR1C3 0.0747
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0644
2164 Multidrug resistance-associated protein 4 ABCC4 0.0603
6167 Organic solute transporter subunit beta OSTB 0.052
6166 Organic solute transporter subunit alpha OSTA 0.0519
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.0405
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0369
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0367
1024 Solute carrier family 22 member 11 SLC22A11 0.0307
6143 Solute carrier family 22 member 7 SLC22A7 0.0304
3811 Cytochrome P450 19A1 CYP19A1 0.0302
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0279
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0278
6144 Solute carrier family 22 member 2 SLC22A2 0.0277
6145 Solute carrier family 22 member 1 SLC22A1 0.0265
6142 Solute carrier family 22 member 8 SLC22A8 0.0263
1729 Solute carrier family 22 member 6 SLC22A6 0.024
4200 Cytochrome P450 1A2 CYP1A2 0.0206
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