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Identification
NameDinoprost Tromethamine
Accession NumberDB01160  (APRD00926)
TypeSmall Molecule
GroupsApproved, Vet Approved
Description

The tromethamine (THAM) salt of the naturally occurring prostaglandin F2 alpha, dinoprost tromethamine occurs as a white to off-white, very hygroscopic, crystalline powder. Dinoprost tromethamine may also be known as dinoprost trometamol, PGF2 alpha THAM, or prostaglandin F2 alpha tromethamine.

Structure
Thumb
Synonyms
Dinoprost trometamol
PGF2-alpha THAM
PGF2alpha THAM
Prostaglandin F2-alpha THAM
Prostaglandin F2a tromethamine
Prostaglandin F2alpha tham
Prostin F2 Alpha
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Prostin F2 Alphasolution5 mgintra-amnioticPfizer Canada Inc1974-12-31Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
DinolyticPfizer
Enzaprost FChinoin
ProsmonFuji Yakuhin
Prostin F2 AlphaPfizer
Brand mixturesNot Available
SaltsNot Available
Categories
UNIICT6BBQ5A68
CAS number38562-01-5
WeightAverage: 475.616
Monoisotopic: 475.314517421
Chemical FormulaC24H45NO8
InChI KeyInChIKey=IYGXEHDCSOYNKY-RZHHZEQLSA-N
InChI
InChI=1S/C20H34O5.C4H11NO3/c1-2-3-6-9-15(21)12-13-17-16(18(22)14-19(17)23)10-7-4-5-8-11-20(24)25;5-4(1-6,2-7)3-8/h4,7,12-13,15-19,21-23H,2-3,5-6,8-11,14H2,1H3,(H,24,25);6-8H,1-3,5H2/b7-4-,13-12+;/t15-,16+,17+,18-,19+;/m0./s1
IUPAC Name
(5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S)-3-hydroxyoct-1-en-1-yl]cyclopentyl]hept-5-enoic acid; 2-amino-2-(hydroxymethyl)propane-1,3-diol
SMILES
OCC(N)(CO)CO.CCCCC[[email protected]](O)\C=C\[[email protected]]1[[email protected]](O)C[[email protected]](O)[C@@H]1C\C=C/CCCC(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as prostaglandins and related compounds. These are unsaturated carboxylic acids consisting of a 20 carbon skeleton that also contains a five member ring, and are based upon the fatty acid arachidonic acid.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassEicosanoids
Direct ParentProstaglandins and related compounds
Alternative Parents
Substituents
  • Prostaglandin skeleton
  • Long-chain fatty acid
  • Hydroxy fatty acid
  • Carbocyclic fatty acid
  • Fatty acid
  • Unsaturated fatty acid
  • Cyclopentanol
  • Cyclic alcohol
  • Secondary alcohol
  • 1,2-aminoalcohol
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Alcohol
  • Aliphatic homomonocyclic compound
  • Aliphatic acyclic compound
Molecular FrameworkNot Available
External DescriptorsNot Available
Pharmacology
IndicationUsed for aborting second-trimester pregnancy (between the twelfth to eighteenth week of gestation) and in incomplete abortion or for therapeutic abortion in cases of intrauterine fetal death and congenital abnormalities incompatible with life. Also used at low-doses for medically indicated induction of labor at term. Also injected intra-arterially for use as a vasodilator to assist in angiography.
PharmacodynamicsDinoprost tromethamine is the tromethamine (THAM) salt of the naturally occurring prostaglandin F2alpha. Prostaglandin F2alpha has several pharmacologic effects on the female reproductive system, including stimulation of myometrial activity, relaxation of the cervix, inhibition of steroidogenesis by corpora lutea, and can potentially lyse corpora lutea.
Mechanism of actionDinoprost tromethamine appears to act directly on the myometrium, but this has not been completely established. Dinoprost stimulates myometrial contractions (via its interaction with the prostaglandin receptors) in the gravid uterus that are similar to the contractions that occur in the term uterus during labor. These contractions are usually sufficient to cause abortion. Uterine response to prostaglandins increases gradually throughout pregnancy. Dinoprost also facilitates cervical dilatation and softening.
Related Articles
AbsorptionSlowly absorbed from the amniotic fluid into systemic circulation.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Enzymatic dehydrogenation primarily in the maternal lungs and also in the liver.

Route of eliminationNot Available
Half lifeThe half-life of dinoprost in amniotic fluid is 3 to 6 hours. The plasma half-life of dinoprost after intravenous administration is reported to be less than 1 minute.
ClearanceNot Available
ToxicityAlthough overdose by intra-amniotic administration of dinoprost has not been reported, exaggeration of the nausea, vomiting, and diarrhea that occur with normal doses would be expected.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9588
Blood Brain Barrier-0.6473
Caco-2 permeable-0.674
P-glycoprotein substrateSubstrate0.6903
P-glycoprotein inhibitor INon-inhibitor0.9204
P-glycoprotein inhibitor IINon-inhibitor0.9821
Renal organic cation transporterNon-inhibitor0.8743
CYP450 2C9 substrateNon-substrate0.838
CYP450 2D6 substrateNon-substrate0.7753
CYP450 3A4 substrateNon-substrate0.5576
CYP450 1A2 substrateNon-inhibitor0.6725
CYP450 2C9 inhibitorNon-inhibitor0.9145
CYP450 2D6 inhibitorNon-inhibitor0.764
CYP450 2C19 inhibitorNon-inhibitor0.8258
CYP450 3A4 inhibitorNon-inhibitor0.9349
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9466
Ames testNon AMES toxic0.9033
CarcinogenicityNon-carcinogens0.9383
BiodegradationNot ready biodegradable0.7399
Rat acute toxicity2.1479 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9677
hERG inhibition (predictor II)Non-inhibitor0.8921
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Solutionintra-amniotic5 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point100-101Morozowich, W.; U.S. Patent 3,657,327; April 18,1972; assigned to The Upjohn Company.
water solubility0.2 g/mLNot Available
logP-0.12Not Available
Predicted Properties
PropertyValueSource
logP2.61ChemAxon
pKa (Strongest Acidic)4.36ChemAxon
pKa (Strongest Basic)-1.6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area97.99 Å2ChemAxon
Rotatable Bond Count15ChemAxon
Refractivity100.47 m3·mol-1ChemAxon
Polarizability41.56 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Morozowich, W.; U.S. Patent 3,657,327; April 18,1972; assigned to The Upjohn Company.

General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS Codes
  • 76:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (51.3 KB)
Interactions
Drug InteractionsNo interactions found.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Prostaglandin f receptor activity
Specific Function:
Receptor for prostaglandin F2-alpha (PGF2-alpha). The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. Initiates luteolysis in the corpus luteum (By similarity). Isoforms 2 to 7 do not bind PGF2-alpha but are proposed to modulate signaling by participating in variant receptor complexes; heterodimers between isoform 1 and ...
Gene Name:
PTGFR
Uniprot ID:
P43088
Molecular Weight:
40054.1 Da
References
  1. Sakamoto K, Kamimura M, Kurozumi S, Ito S: Prostaglandin F2 alpha receptor. J Lipid Mediat Cell Signal. 1995 Oct;12(2-3):405-11. [PubMed:8777582 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Guanyl-nucleotide exchange factor activity
Specific Function:
Receptor for prostacyclin (prostaglandin I2 or PGI2). The activity of this receptor is mediated by G(s) proteins which activate adenylate cyclase.
Gene Name:
PTGIR
Uniprot ID:
P43119
Molecular Weight:
40955.485 Da
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:17139284 ]
  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:17016423 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Quaternary ammonium group transmembrane transporter activity
Specific Function:
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridiniu...
Gene Name:
SLC22A2
Uniprot ID:
O15244
Molecular Weight:
62579.99 Da
References
  1. Kimura H, Takeda M, Narikawa S, Enomoto A, Ichida K, Endou H: Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8. [PubMed:11907186 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-in...
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
References
  1. Kimura H, Takeda M, Narikawa S, Enomoto A, Ichida K, Endou H: Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8. [PubMed:11907186 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha-ketoglutarate.
Gene Name:
SLC22A7
Uniprot ID:
Q9Y694
Molecular Weight:
60025.025 Da
References
  1. Kimura H, Takeda M, Narikawa S, Enomoto A, Ichida K, Endou H: Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8. [PubMed:11907186 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
Molecular Weight:
59855.585 Da
References
  1. Kimura H, Takeda M, Narikawa S, Enomoto A, Ichida K, Endou H: Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8. [PubMed:11907186 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
Gene Name:
SLC22A11
Uniprot ID:
Q9NSA0
Molecular Weight:
59970.945 Da
References
  1. Kimura H, Takeda M, Narikawa S, Enomoto A, Ichida K, Endou H: Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8. [PubMed:11907186 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
May mediate the release of newly synthesized prostaglandins from cells, the transepithelial transport of prostaglandins, and the clearance of prostaglandins from the circulation. Transports PGD2, as well as PGE1, PGE2 and PGF2A.
Gene Name:
SLCO2A1
Uniprot ID:
Q92959
Molecular Weight:
70043.33 Da
References
  1. Lu R, Kanai N, Bao Y, Schuster VL: Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA(hPGT). J Clin Invest. 1996 Sep 1;98(5):1142-9. [PubMed:8787677 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent transport of organic anions such as estrone-3-sulfate (PubMed:10873595). Mediates transport of prostaglandins (PG) E1 and E2, thyroxine (T4), deltorphin II, BQ-123 and vasopressin, but not DPDPE (a derivative of enkephalin lacking an N-terminal tyrosine residue), estrone-3-sulfate, taurocholate, digoxin nor DHEAS (PubMed:16971491).
Gene Name:
SLCO3A1
Uniprot ID:
Q9UIG8
Molecular Weight:
76552.135 Da
References
  1. Adachi H, Suzuki T, Abe M, Asano N, Mizutamari H, Tanemoto M, Nishio T, Onogawa T, Toyohara T, Kasai S, Satoh F, Suzuki M, Tokui T, Unno M, Shimosegawa T, Matsuno S, Ito S, Abe T: Molecular characterization of human and rat organic anion transporter OATP-D. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1188-97. [PubMed:14631946 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23