Identification

Name
Gemeprost
Accession Number
DB08964
Type
Small Molecule
Groups
Approved, Withdrawn
Description

Gemeprost is a prostaglandin E1 (PGE1) analog and antiprogestogen used for preoperative dilation of the cervix before surgical abortion. It is available as vaginal suppositories and also used in combination with the antiprogestin and mifepristone for termination of 1st- and 2nd-trimester pregnancy [1]. It is not FDA-approved but available in Japan marketed as Preglandin.

Structure
Thumb
Synonyms
  • 16,16-Dimethyl-trans-delta-2-PGE1 methyl ester
  • 16,16-Dimethyl-trans-delta(sup 2)-prostaglandin E1 methyl ester
  • SC-37681
External IDs
SC-37681
International/Other Brands
Cergem (MSD Merck Sharp & Dohme) / Cervagem (Sanofi) / Cervagème (Sanofi-Aventis) / Cervidil (Merck Serono)
Categories
UNII
45KZB1FOLS
CAS number
64318-79-2
Weight
Average: 394.552
Monoisotopic: 394.271924324
Chemical Formula
C23H38O5
InChI Key
KYBOHGVERHWSSV-VNIVIJDLSA-N
InChI
InChI=1S/C23H38O5/c1-5-6-15-23(2,3)21(26)14-13-18-17(19(24)16-20(18)25)11-9-7-8-10-12-22(27)28-4/h10,12-14,17-18,20-21,25-26H,5-9,11,15-16H2,1-4H3/b12-10+,14-13+/t17-,18-,20-,21-/m1/s1
IUPAC Name
methyl (2E)-7-[(1R,2R,3R)-3-hydroxy-2-[(1E,3R)-3-hydroxy-4,4-dimethyloct-1-en-1-yl]-5-oxocyclopentyl]hept-2-enoate
SMILES
CCCCC(C)(C)[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCC\C=C\C(=O)OC

Pharmacology

Indication

Indicated for the softening and dilatation of the cervix uteri prior to transcervical, intrauterine operative procedures in the first trimester of pregnancy or facilitating therapeutic termination of pregnancy in patients in the second trimester of gestation.

Pharmacodynamics

Gemeprost softens and dilates of the cervix prior to transcervical intrauterine operative procedures. It is a prostaglandin E1 analog that potently stimulates uterine contractions and causes cervical ripening and relaxation [1].

Mechanism of action

As a prostaglandin analog, gemeprost binds to prostaglandin E2 and E3 receptors as an agonist to cause myometrial contractions and progressive cervical dilation via tissue sensitization to oxytocin [4].

TargetActionsOrganism
UProstaglandin E2 receptor EP2 subtype
agonist
Human
AProstaglandin E2 receptor EP3 subtype
agonist
Human
Absorption

Systemic absorption of gemeprost is limited with about 12-28% of administered dose of gemeprost reaching the systemic circulation [5]. Following vaginal administration, peak plasma concentration is reached after 2-3 hours [1].

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

After intravenous administration, gemeprost is rapidly metabolized via hydrolysis to the free acid with half life of 10-15 minutes. The free acid is then inactivated by β- and ω-oxidation [1].

Route of elimination

About 50% of the dose eliminated as metabolites in the urine during the first 24 hours.

Half life
Not Available
Clearance
Not Available
Toxicity

Serious or life-threatening adverse effects include coronary spasms with subsequent myocardial infarctions and uterine rupture following prolonged uterine hypertonia or abnormal uterine pain. More common adverse effects are nausea, vomiting, loose stools, diarrhea, lower abdominal or back pain, headache, mild pyrexia and flushing. Less common side effects include hypotension, chest pain palpitations, tachycardia, muscle weakness, dyspnea, chills and headache. Oral LD50 is 300 mg/kg in mouse, 980 mg/kg in rat and 3200 mg/kg in rabbit [MSDS].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Gemeprost which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Gemeprost which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Gemeprost which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Gemeprost which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Gemeprost which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Gemeprost which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Gemeprost which could result in a higher serum level.
AcrivastineGemeprost may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Gemeprost which could result in a higher serum level.
AdefovirAdefovir may decrease the excretion rate of Gemeprost which could result in a higher serum level.
Food Interactions
Not Available

References

Synthesis Reference

U.S. Patent 4,052,512.

General References
  1. Bygdeman M: Pharmacokinetics of prostaglandins. Best Pract Res Clin Obstet Gynaecol. 2003 Oct;17(5):707-16. [PubMed:12972009]
  2. Bartley J, Baird DT: A randomised study of misoprostol and gemeprost in combination with mifepristone for induction of abortion in the second trimester of pregnancy. BJOG. 2002 Nov;109(11):1290-4. [PubMed:12452468]
  3. Wong KS, Ngai CS, Wong AY, Tang LC, Ho PC: Vaginal misoprostol compared with vaginal gemeprost in termination of second trimester pregnancy. A randomized trial. Contraception. 1998 Oct;58(4):207-10. [PubMed:9866000]
  4. Husslein P: [Causes of labor initiation in man: role of oxytocin and prostaglandins]. Z Geburtshilfe Perinatol. 1985 May-Jun;189(3):95-102. [PubMed:2996248]
  5. CERVAGEM (Gemeprost) Product information [Link]
External Links
KEGG Drug
D02073
PubChem Compound
5282237
PubChem Substance
310264927
ChemSpider
4445416
ChEBI
135626
ChEMBL
CHEMBL1908315
Wikipedia
Gemeprost
ATC Codes
G02AD03 — Gemeprost
MSDS
Download (78.8 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0176 mg/mLALOGPS
logP4.02ALOGPS
logP4.71ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)14.68ChemAxon
pKa (Strongest Basic)-1.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area83.83 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity113.05 m3·mol-1ChemAxon
Polarizability46.3 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as fatty alcohols. These are aliphatic alcohols consisting of a chain of a least six carbon atoms.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Fatty Acyls
Sub Class
Fatty alcohols
Direct Parent
Fatty alcohols
Alternative Parents
Fatty acid esters / Cyclopentanols / Methyl esters / Enoate esters / Cyclic ketones / Cyclic alcohols and derivatives / Monocarboxylic acids and derivatives / Organic oxides / Hydrocarbon derivatives
Substituents
Fatty alcohol / Fatty acid ester / Cyclopentanol / Cyclic alcohol / Methyl ester / Enoate ester / Alpha,beta-unsaturated carboxylic ester / Secondary alcohol / Ketone / Carboxylic acid ester
Molecular Framework
Aliphatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Prostaglandin e receptor activity
Specific Function
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 ...
Gene Name
PTGER2
Uniprot ID
P43116
Uniprot Name
Prostaglandin E2 receptor EP2 subtype
Molecular Weight
39759.945 Da
References
  1. Matsuya H, Sekido N, Kida J, Mashimo H, Wakamatsu D, Okada H: Effects of an EP2 and EP3 Receptor Dual Agonist, ONO-8055, on a Radical Hysterectomy-Induced Underactive Bladder Model in Monkeys. Low Urin Tract Symptoms. 2017 Apr 25. doi: 10.1111/luts.12166. [PubMed:28439968]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Rna polymerase ii transcription factor activity, ligand-activated sequence-specific dna binding
Specific Function
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 ...
Gene Name
PTGER3
Uniprot ID
P43115
Uniprot Name
Prostaglandin E2 receptor EP3 subtype
Molecular Weight
43309.335 Da
References
  1. Qian YM, Jones RL, Chan KM, Stock AI, Ho JK: Potent contractile actions of prostanoid EP3-receptor agonists on human isolated pulmonary artery. Br J Pharmacol. 1994 Oct;113(2):369-74. [PubMed:7834185]
  2. Matsuya H, Sekido N, Kida J, Mashimo H, Wakamatsu D, Okada H: Effects of an EP2 and EP3 Receptor Dual Agonist, ONO-8055, on a Radical Hysterectomy-Induced Underactive Bladder Model in Monkeys. Low Urin Tract Symptoms. 2017 Apr 25. doi: 10.1111/luts.12166. [PubMed:28439968]

Drug created on June 09, 2014 09:01 / Updated on November 02, 2018 06:56