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| Clinical data | |
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| Other names | Amoglandin, Croniben, Cyclosin, Dinifertin, Enzaprost, Glandin, PGF2α, Panacelan, Prostamodin |
| AHFS/Drugs.com | International Drug Names |
| Routes of administration | Intravenous (cannot used to induce labor)because it cannot be used in cervix,intra-amniotic (to induce abortion) |
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| Pharmacokinetic data | |
| Eliminationhalf-life | 3 to 6 hours inamniotic fluid, less than 1 minute inblood plasma |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.209.720 |
| Chemical and physical data | |
| Formula | C20H34O5 |
| Molar mass | 354.487 g·mol−1 |
| 3D model (JSmol) | |
| Solubility in water | 200 mg/mL (20 °C) |
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Prostaglandin F2α (PGF2α inprostanoid nomenclature), pharmaceutically termeddinoprost, is a naturally occurringprostaglandin used in medicine toinduce labor and as anabortifacient.[1] Prostaglandins are lipids throughout the entire body that have a hormone-like function.[2] In pregnancy, PGF2α is medically used to sustain contracture and provoke myometrial ischemia to accelerate labor and prevent significant blood loss in labor.[3] Additionally, PGF2α has been linked to being naturally involved in the process of labor. It has been seen that there are higher levels of PGF2α in maternal fluid during labor when compared to at term.[4] This signifies that there is likely a biological use and significance to the production and secretion of PGF2α in labor. Prostaglandin is also used to treat uterine infections in domestic animals.
In domestic mammals, it is produced by the uterus when stimulated byoxytocin, in the event that there has been no implantation during the luteal phase. It acts on thecorpus luteum to causeluteolysis, forming acorpus albicans and stopping the production of progesterone. Action of PGF2α is dependent on the number of receptors on the corpus luteum membrane.
The PGF2α isoform8-iso-PGF2α was found in significantly increased amounts in patients withendometriosis, thus being a potential causative link in endometriosis-associatedoxidative stress.[5]
PGF2α acts by binding to theprostaglandin 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.[6] 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.[7] PGF2α and oxytocin also inhibit the production ofprogesterone, 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.[8]
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),[9] 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.
Lutalyse is used for the treatment ofpyometra in domestic dogs and cats.[10] The drug is also administered to dairy cows in order to reduce uterine infections.[11]
In 2012 a concise and highly stereoselective total synthesis of PGF2α was described.[12] The synthesis requires only seven steps, a huge improvement on the original 17-step synthesis of Corey,[13] and uses 2,5-dimethoxytetrahydrofuran as a starting reagent, withS-proline as an asymmetric catalyst.
In 2019, a more effective and stereoselective synthesis was described.[14] 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 toarachidonic acid, the framework from which all prostaglandins are formed.[15] Arachidonic acid then reacts with twocyclooxygenase (COX) receptors, COX-1 and COX-2, or PGH synthase to form prostaglandin H2, an intermediate.[15] Lastly, the compound reacts withaldose reductase orprostaglandin F synthase to form PGF2α.[15]
The following medications areanalogues of prostaglandin F2α: