Prostaglandin F2alpha

Mechanism of action

PGF2α 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. Because PGF2α is linked with an increase in uterine oxytocin levels, there is evidence that PGF2α and oxytocin form a positive feedback loop to facilitate the degradation of the corpus luteum. PGF2α and oxytocin also inhibit the production of progesterone, a hormone that facilitates corpus luteum development. Conversely, higher progesterone levels inhibit production of PGF2α and oxytocin, as the effects of the hormones are in opposition to each other. This is directly exhibited following ovulation when there is a spike of progesterone levels, and then as progesterone levels decrease, PGF2α levels will peak.

Pharmaceutical Use

When injected into the body or amniotic sac, PGF2α can either induce labor or cause an abortion depending on the concentration used. In small doses (1–4 mg/day), PGF2α acts to stimulate uterine muscle contractions, which aids in the birth process. However, during the first trimester and in higher concentrations (40 mg/day), PGF2α can cause an abortion by degrading the corpus luteum, which normally acts to maintain pregnancy via the production of progesterone. Since the fetus is not viable outside the womb by this time, the lack of progesterone leads to the shedding of the uterine lining and the death of the fetus. However, this process is not fully understood.

Pyometra and uterine infections

Lutalyse is used for the treatment of pyometra in domestic dogs and cats. The drug is also administered to dairy cows in order to reduce uterine infections.

Synthesis

Industrial Synthesis

In 2012 a concise and highly stereoselective total synthesis of PGF2α was described. The synthesis requires only seven steps, a huge improvement on the original 17-step synthesis of Corey, and uses 2,5-dimethoxytetrahydrofuran as a starting reagent, with S-proline as an asymmetric catalyst.

In 2019, a more effective and stereoselective synthesis was described. The synthesis requires 5 steps to get to the intermediate which then undergoes a cross-metathesis reaction to install the E-alkene. Then, a Wittig reaction is performed to install the Z-alkene. Finally, the protecting groups are removed with acid.

In the body PGF2α 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. Arachidonic acid then reacts with two cyclooxygenase (COX) receptors, COX-1 and COX-2, or PGH synthase to form prostaglandin H2, an intermediate. Lastly, the compound reacts with aldose reductase or prostaglandin F synthase to form PGF2α.

Analogues

The following medications are analogues of prostaglandin F2α:

• Latanoprost
• Bimatoprost
• Travoprost
• Carboprost

References

References

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8. (2016). "Dinoprost tromethamine Injection Advanced Patient Information".
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10. "Evaluation of Single Lutalyse Injection Protocol to Reduce Uterine Infections and Improve Reproductive Efficiency in Postpartum Dairy Cows.". OREGON STATE UNIVERSITY.
11. (September 2012). "Stereocontrolled organocatalytic synthesis of prostaglandin PGF2α in seven steps". Nature.
12. (1995). "The Logic of Chemical Synthesis". Wiley.
13. (2019). "Total synthesis of PGF2α and 6,15-diketo-PGF1α and formal synthesis of 6-keto-PGF1α via three-component coupling.". Tetrahedron.
14. (August 2008). "A postgenomic integrated view of prostaglandins in reproduction: implications for other body systems". Journal of Physiology and Pharmacology.