Prostaglandin F2alpha

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Dinoprost
Dinoprost.svg
Clinical data
Synonyms Amoglandin, Croniben, Cyclosin, Dinifertin, Enzaprost, Glandin, PGF2α, Panacelan, Prostamodin
AHFS/Drugs.com International Drug Names
Routes of
administration
Intravenous (to induce labor), intra-amniotic (to induce abortion)
ATC code
Pharmacokinetic data
Elimination half-life 3 to 6 hours in amniotic fluid, less than 1 minute in blood plasma
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
KEGG
ChEMBL
ECHA InfoCard 100.209.720 Edit this at Wikidata
Chemical and physical data
Formula C20H34O5
Molar mass 354.48 g/mol
3D model (JSmol)
Solubility in water 200 mg/mL (20 °C)
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Prostaglandin F (PGF in prostanoid nomenclature), pharmaceutically termed dinoprost (INN), is a naturally occurring prostaglandin used in medicine to induce labor and as an abortifacient.[1]

In domestic mammals, it is produced by the uterus when stimulated by oxytocin, in the event that there has been no implantation during the luteal phase. It acts on the corpus luteum to cause luteolysis, forming a corpus albicans and stopping the production of progesterone. Action of PGF is dependent on the number of receptors on the corpus luteum membrane.

The PGF isoform 8-iso-PGF was found in significantly increased amounts in patients with endometriosis, thus being a potential causative link in endometriosis-associated oxidative stress.[2]

Mechanism of action[edit]

PGF acts by binding to the prostaglandin F2α receptor. It is released in response to an increase in oxytocin levels in the uterus, and stimulates both luteolytic activity and the release of oxytocin.[3] Because PGF is linked with an increase in uterine oxytocin levels, there is evidence that PGF and oxytocin form a positive feedback loop to facilitate the degradation of the corpus luteum.[4] PGF and oxytocin also inhibit the production of progesterone, a hormone that facilitates corpus luteum development. Conversely, higher progesterone levels inhibit production of PGF and oxytocin, as the effects of the hormones are in opposition to each other.

Pharmaceutical Use[edit]

When injected into the body or amniotic sac, PGF can either induce labor or cause an abortion depending on the concentration used. In small doses (1–4 mg/day), PGF acts to stimulate uterine muscle contractions, which aids in the birth process. However, during the second trimester and in higher concentrations (40 mg/day),[5] PGF can cause an abortion by degrading the corpus luteum, which nourishes the fetus in the womb. Since the fetus is not viable outside the womb by this time, the lack of sustenance starves and aborts the fetus after a day or two.

Synthesis[edit]

Industrial Synthesis[edit]

In 2012 a concise and highly stereoselective total synthesis of PGF was described.[6] The synthesis requires only seven steps, a huge improvement on the original 17-steps synthesis of Corey and Cheng,[7] and uses 2,5-dimethoxytetrahydrofuran as a starting reagent, with S-proline as an asymmetric catalyst.

Biosynthesis[edit]

In the body PGF is synthesized in several distinct steps. First, Phospholipase A2 (PLA2) facilitates the conversion of phospholipids to Arachidonic Acid, the framework from which all prostaglandins are formed.[8] The Arachidonic Acid then reacts with two Cyclooxygenase (COX) receptors, COX-1 and COX-2 to form Prostaglandin H2, an intermediate. Lastly, the compound reacts with Aldose Reductase (AKR1B1) to form PGF.[8]

Analogues[edit]

The following medications are analogues of prostaglandin F:

References[edit]

  1. ^ The Merck index : an encyclopedia of chemicals, drugs, and biologicals. O'Neil, Maryadele J., Royal Society of Chemistry (Great Britain) (15th ed.). Cambridge, UK: Royal Society of Chemistry. 2013. ISBN 1849736707. OCLC 824530529. 
  2. ^ Sharma, I.; Dhaliwal, L.; Saha, S.; Sangwan, S.; Dhawan, V. (2010). "Role of 8-iso-prostaglandin F2alpha and 25-hydroxycholesterol in the pathophysiology of endometriosis". Fertility and Sterility. 94 (1): 63–70. doi:10.1016/j.fertnstert.2009.01.141. PMID 19324352. 
  3. ^ Samuelsson, B.; Goldyne, M.; Granström, E.; et al. (1978). "Prostaglandins and thromboxanes". Annual Review of Biochemistry. 47: 997–1029. doi:10.1146/annurev.bi.47.070178.005025. 
  4. ^ Hooper, S.B.; Watkins, W.B.; Thorburn, G.D. (1986). "Oxytocin, oxytocin associated neurophysin, and prostaglandin F2 a concentrations in the uteroovarian vein of pregnant and nonpregnant sheep". Endocrinology. 119: 2590–2597. doi:10.1210/endo-119-6-2590. 
  5. ^ "Dinoprost tromethamine Injection Advanced Patient Information". Truvn Health Analytics Inc. 2016. Retrieved November 2, 2017. 
  6. ^ Coulthard, G.; Erb, W.; Aggarwal, V. K. (2012). "Stereocontrolled organocatalytic synthesis of prostaglandin PGF2α in seven steps". Nature. 489 (7415): 278–281. doi:10.1038/nature11411. PMID 22895192. 
  7. ^ Corey, E.J.; Cheng, X.M. (1995). The Logic of Chemical Synthesis. Wiley. 
  8. ^ a b Fortier, M. A.; Krishnaswamy, K.; Danyod, G.; Boucher-Kovalik, S.; Chapdalaine, P. (August 2008). "A postgenomic integrated view of prostaglandins in reproduction: implications for other body systems". Journal of Physiology and Pharmacology. 59 Suppl 1: 65–89. ISSN 1899-1505. PMID 18802217.