| Revision as of 17:18, 6 January 2011 edit41.238.20.188 (talk) →Mechanism of action← Previous edit |
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{{Short description|Chemical compound}} |
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{{About|the pharmaceutical agent 'dinoprost'|the drug 'dinoprostone'|Prostaglandin E2}} |
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{{About|the pharmaceutical agent 'dinoprost'|the drug 'dinoprostone'|Prostaglandin E2}} |
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{{drugbox |
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{{Drugbox |
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| Verifiedfields = changed |
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| verifiedrevid = 378530557 |
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| Watchedfields = changed |
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|IUPAC_name=(''Z'')-7-cyclopentyl]hept-5-enoic acid |
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| verifiedrevid = 406310380 |
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|image=Dinoprost.svg |
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| IUPAC_name = (''Z'')-7-cyclopentyl]hept-5-enoic acid |
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|CASNo_Ref = {{cascite}} |
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| image = Dinoprost.svg |
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| CAS_number=551-11-1 |
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| drug_name = Dinoprost |
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|CAS_supplemental={{CAS|38562-01-5}} (]) |
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<!--Clinical data--> |
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|ATC_prefix=G02 |
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| tradename = |
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|ATC_suffix=AD01 |
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| Drugs.com = {{drugs.com|international|dinoprost-tromethamine}} |
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|ATC_supplemental= |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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|PubChem=5280363 |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| IUPHAR_ligand = 1957 |
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| legal_AU = <!-- Unscheduled / S2 / S4 / S8 --> |
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| legal_UK = <!-- GSL / P / POM / CD --> |
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| legal_US = <!-- OTC / Rx-only --> |
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| routes_of_administration = ] (cannot used to induce labor)because it cannot be used in cervix, ] (to induce abortion) |
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<!--Pharmacokinetic data--> |
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| elimination_half-life = 3 to 6 hours in ], less than 1 minute in ] |
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<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 551-11-1 |
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| CAS_supplemental = {{CAS|38562-01-5}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = B7IN85G1HY |
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| ATC_prefix = G02 |
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| ATC_suffix = AD01 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 4444062 |
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| smiles = O=C(O)CCC/C=C\C1(O)C(O)1/C=C/(O)CCCCC |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 1S/C20H34O5/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/h4,7,12-13,15-19,21-23H,2-3,5-6,8-11,14H2,1H3,(H,24,25)/b7-4-,13-12+/t15-,16+,17+,18-,19+/m0/s1 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = PXGPLTODNUVGFL-YNNPMVKQSA-N |
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| PubChem = 5280363 |
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| IUPHAR_ligand = 1884 |
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| IUPHAR_ligand = 1884 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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|DrugBank=DB01160 |
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| DrugBank = DB01160 |
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|C=20|H=34|O=5 |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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|molecular_weight=354.48 g/mol |
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| KEGG = D00081 |
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|smiles=CCCCC(\C=C\1(C(1C\C=C/CCCC(=O)O)O)O)O |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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|bioavailability= |
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| ChEMBL = 815 |
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|protein_bound= |
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<!--Chemical data--> |
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|metabolism= |
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| C=20 | H=34 | O=5 |
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|elimination_half-life=3 to 6 hours in ], less than 1 minute in ] |
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|alt=|caption=|type=|MedlinePlus=|legal_status=|licence_EU=|pregnancy_category=|licence_US=|solubility=200|synonyms=Amoglandin, Croniben, Cyclosin, Dinifertin, Enzaprost, Glandin, PGF2α, Panacelan, Prostamodin}} |
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|excretion= |
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'''Prostaglandin F<sub>2α</sub>''' ('''PGF<sub>2α</sub>''' in ] nomenclature), pharmaceutically termed '''dinoprost''', is a naturally occurring ] used in medicine to ] and as an ].<ref>{{Cite book|title=The Merck index: an encyclopedia of chemicals, drugs, and biologicals.|date=2013|publisher=Royal Society of Chemistry| veditors = O'Neil MJ |isbn=978-1849736701|edition=15th|location=Cambridge, UK|oclc=824530529}}</ref> Prostaglandins are lipids throughout the entire body that have a hormone-like function.<ref>{{Cite web|url= https://www.britannica.com/science/prostaglandin|title=Prostaglandin|date=September 28, 2022|website= Britannica|access-date= November 6, 2022 |
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|pregnancy_AU=<!-- A / B1 / B2 / B3 / C / D / X --> |
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|pregnancy_US=<!-- A / B / C / D / X --> |
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|pregnancy_category= |
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|legal_AU=<!-- Unscheduled / S2 / S4 / S8 --> |
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|legal_UK=<!-- GSL / P / POM / CD --> |
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|legal_US=<!-- OTC / Rx-only --> |
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|legal_status= |
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|routes_of_administration=] (to induce labor), ] (to induce abortion) |
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}} |
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'''] F<sub>2α</sub>''' ('''PGF<sub>2α</sub>''' in ] nomenclature) is pharmaceutically termed '''Dinoprost''' (]) is a naturally-occurring prostaglandin used in medicine to ] and as an ]. |
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}}</ref> In pregnancy, PGF<sub>2α</sub> is medically used to sustain contracture and provoke myometrial ischemia to accelerate labor and prevent significant blood loss in labor.<ref>{{cite journal | vauthors = Kerekes L, Domokos N | title = The effect of prostaglandin F2 alpha on third stage labor | journal = Prostaglandins | volume = 18 | issue = 1 | pages = 161–166 | date = July 1979 | pmid = 392622 | doi = 10.1016/S0090-6980(79)80034-9 }}</ref> Additionally, PGF<sub>2α</sub> has been linked to being naturally involved in the process of labor. It has been seen that there are higher levels of PGF<sub>2α</sub> in maternal fluid during labor when compared to at term.<ref>{{cite journal | vauthors = Sahmay S, Coke A, Hekim N, Atasu T | title = Maternal, umbilical, uterine and amniotic prostaglandin E and F2 alpha levels in labour | journal = The Journal of International Medical Research | volume = 16 | issue = 4 | pages = 280–285 | date = 1988 | pmid = 3169373 | doi = 10.1177/030006058801600405 | s2cid = 73028858 }}</ref> This signifies that there is likely a biological use and significance to the production and secretion of PGF<sub>2α</sub> in labor. Prostaglandin is also used to treat uterine infections in domestic animals. |
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In domestic mammals, it is produced by the uterus when stimulated by ], in the event that there has been no implantation during the follicular phase. It acts on the ] to cause ], forming a ] and stopping the production of progesterone. Action of PGF<sub>2α</sub> is dependent on the number of receptors on the corpus luteum membrane. |
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In domestic mammals, it is produced by the uterus when stimulated by ], in the event that there has been no implantation during the luteal phase. It acts on the ] to cause ], forming a ] and stopping the production of progesterone. Action of PGF<sub>2α</sub> is dependent on the number of receptors on the corpus luteum membrane. |
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The PGF<sub>2α</sub> isoform ''8-iso-PGF<sub>2α</sub>'' is significantly increased ], being a potential causative links in endometriosis-associated oxidative stress.<ref>{{cite doi|10.1016/j.fertnstert.2009.01.141}}</ref> |
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The PGF<sub>2α</sub> isoform ''8-iso-PGF<sub>2α</sub>'' was found in significantly increased amounts in patients with ], thus being a potential causative link in endometriosis-associated oxidative stress.<ref>{{cite journal | vauthors = Sharma I, Dhaliwal LK, Saha SC, Sangwan S, Dhawan V | title = Role of 8-iso-prostaglandin F2alpha and 25-hydroxycholesterol in the pathophysiology of endometriosis | journal = Fertility and Sterility | volume = 94 | issue = 1 | pages = 63–70 | date = June 2010 | pmid = 19324352 | doi = 10.1016/j.fertnstert.2009.01.141 | doi-access = free }}</ref> |
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==Mechanism of action== |
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==Mechanism of action== |
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{{further|]}} |
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{{further|Prostaglandin F2α receptor}} |
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PGF<sub>2α</sub> acts by binding to the ]. It is released in response to an increase in oxytocin levels in the uterus, and stimulates both luteolytic activity and the release of oxytocin.<ref>{{cite journal | vauthors = Samuelsson B, Goldyne M, Granström E, Hamberg M, Hammarström S, Malmsten C | title = Prostaglandins and thromboxanes | journal = Annual Review of Biochemistry | volume = 47 | pages = 997–1029 | date = 1978 | pmid = 209733 | doi = 10.1146/annurev.bi.47.070178.005025 }}</ref> Because PGF<sub>2α</sub> is linked with an increase in uterine oxytocin levels, there is evidence that PGF<sub>2α</sub> and oxytocin form a positive feedback loop to facilitate the degradation of the corpus luteum.<ref>{{cite journal | vauthors = Hooper SB, Watkins WB, Thorburn GD | title = Oxytocin, oxytocin-associated neurophysin, and prostaglandin F2 alpha concentrations in the utero-ovarian vein of pregnant and nonpregnant sheep | journal = Endocrinology | volume = 119 | issue = 6 | pages = 2590–2597 | date = December 1986 | pmid = 3465529 | doi = 10.1210/endo-119-6-2590 | url = https://tede.ufrrj.br/jspui/handle/jspui/2269 }}</ref> PGF<sub>2α</sub> and oxytocin also inhibit the production of ], a hormone that facilitates corpus luteum development. Conversely, higher progesterone levels inhibit production of PGF<sub>2α</sub> 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, PGF<sub>2α</sub> levels will peak.<ref>{{cite journal | vauthors = Downie J, Poyser NL, Wunderlich M | title = Levels of prostaglandins in human endometrium during the normal menstrual cycle | journal = The Journal of Physiology | volume = 236 | issue = 2 | pages = 465–472 | date = January 1974 | pmid = 16992446 | pmc = 1350813 | doi = 10.1113/jphysiol.1974.sp010446 }}</ref> |
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PGF<sub>2α</sub> acts by binding to the ].it is also commercially available as (Enzaprost) |
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== Pharmaceutical Use == |
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==References== |
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When injected into the body or amniotic sac, PGF<sub>2α</sub> can either induce labor or cause an abortion depending on the concentration used. In small doses (1–4 mg/day), PGF<sub>2α</sub> acts to stimulate uterine muscle contractions, which aids in the birth process. However, during the first trimester and in higher concentrations (40 mg/day),<ref>{{Cite web|url=https://www.drugs.com/cons/dinoprost-tromethamine-injection.html.|title=Dinoprost tromethamine Injection Advanced Patient Information|date=2016|website=Truvn Health Analytics Inc.|access-date=November 2, 2017}}</ref> PGF<sub>2α</sub> 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. |
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{{reflist}} |
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==Pyometra and uterine infections== |
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Lutalyse is used for the treatment of ] in domestic dogs and cats.<ref name="NLM">{{cite journal | vauthors = Davidson AP, Feldman EC, Nelson RW | title = Treatment of pyometra in cats, using prostaglandin F2 alpha: 21 cases (1982-1990) | journal = Journal of the American Veterinary Medical Association | volume = 200 | issue = 6 | pages = 825–828 | date = March 1992 | pmid = 1568932 | url = https://pubmed.ncbi.nlm.nih.gov/1568932/ | access-date = 2 December 2021 | publisher = National Library of Medicine | doi = 10.2460/javma.1992.200.06.825 }}</ref> The drug is also administered to dairy cows in order to reduce uterine infections.<ref name="MENINO">{{cite web | vauthors = Menino A |title=Evaluation of Single Lutalyse Injection Protocol to Reduce Uterine Infections and Improve Reproductive Efficiency in Postpartum Dairy Cows. |url=https://reeis.usda.gov/web/crisprojectpages/0229915-evaluation-of-a-single-lutalyse-injection-protocol-to-reduce-uterine-infections-and-improve-reproductive-efficiency-in-postpartum-dairy-cows.html |website=USDA |publisher=OREGON STATE UNIVERSITY |access-date=2 December 2021}}</ref> |
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==Synthesis== |
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=== Industrial Synthesis === |
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In 2012 a concise and highly stereoselective total synthesis of PGF<sub>2α</sub> was described.<ref name="coulthard2012">{{cite journal | vauthors = Coulthard G, Erb W, Aggarwal VK | title = Stereocontrolled organocatalytic synthesis of prostaglandin PGF2α in seven steps | journal = Nature | volume = 489 | issue = 7415 | pages = 278–281 | date = September 2012 | pmid = 22895192 | doi = 10.1038/nature11411 | s2cid = 205230275 | bibcode = 2012Natur.489..278C }}</ref> The synthesis requires only seven steps, a huge improvement on the original 17-steps synthesis of Corey and Cheng,<ref name="coreybook">{{cite book |title=The Logic of Chemical Synthesis | vauthors = Corey EJ, Cheng XM |publisher=Wiley |year=1995 }}</ref> and uses 2,5-dimethoxytetrahydrofuran as a starting reagent, with ''S''-] as an asymmetric catalyst. |
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In 2019, a more effective and stereoselective synthesis was described.<ref>{{cite journal | vauthors = Kim T, Lee SI, Kim S, Shim SY, Ryu DH | title= Total synthesis of PGF2α and 6,15-diketo-PGF1α and formal synthesis of 6-keto-PGF1α via three-component coupling.| journal = Tetrahedron | volume = 75 | issue = 42 | pages = 130593 | date = 2019 | doi = 10.1016/j.tet.2019.130593| s2cid= 203131829}}</ref> 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. |
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In the body PGF<sub>2α</sub> is synthesized in several distinct steps. First, ] (PLA<sub>2</sub>) facilitates the conversion of phospholipids to ], the framework from which all prostaglandins are formed.<ref name="Fortier_2008">{{cite journal | vauthors = Fortier MA, Krishnaswamy K, Danyod G, Boucher-Kovalik S, Chapdalaine P | title = A postgenomic integrated view of prostaglandins in reproduction: implications for other body systems | journal = Journal of Physiology and Pharmacology | volume = 59 | pages = 65–89 | date = August 2008 | pmid = 18802217 }}</ref> Arachidonic acid then reacts with two ] (COX) receptors, COX-1 and COX-2, or PGH synthase to form prostaglandin H<sub>2</sub>, an intermediate.<ref name="Fortier_2008" /> Lastly, the compound reacts with ] or ] to form PGF<sub>2α</sub>.<ref name="Fortier_2008" /> |
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==Analogues== |
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The following medications are ] of prostaglandin F<sub>2α</sub>: |
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* ] |
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* ] |
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* ] |
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* ] |
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== References == |
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{{Reflist|2}} |
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{{Prostaglandins}} |
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{{Prostaglandins}} |
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{{Oxytocics}} |
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{{Oxytocics}} |
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{{Obstetric drugs}} |
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{{Prostanoidergics}} |
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{{medicine-stub}} |
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