Sulprostone

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Sulprostone
Sulprostone.png
Clinical data
AHFS/Drugs.com International Drug Names
ATC code
Identifiers
  • (Z)-7-[(1R,3R)-3-hydroxy-2-[(E,3R)-3-hydroxy-4-phenoxybut-1-enyl]-5-oxocyclopentyl]-N-methylsulfonylhept-5-enamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.056.503 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C23H31NO7S
Molar mass 465.56 g·mol−1
3D model (JSmol)
  • CS(=O)(=O)NC(=O)CCC/C=C\C[C@@H]1[C@H]([C@@H](CC1=O)O)/C=C/[C@H](COc2ccccc2)O
  • InChI=1S/C23H31NO7S/c1-32(29,30)24-23(28)12-8-3-2-7-11-19-20(22(27)15-21(19)26)14-13-17(25)16-31-18-9-5-4-6-10-18/h2,4-7,9-10,13-14,17,19-20,22,25,27H,3,8,11-12,15-16H2,1H3,(H,24,28)/b7-2-,14-13+/t17-,19-,20-,22-/m1/s1 X mark.svgN
  • Key:UQZVCDCIMBLVNR-TWYODKAFSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Sulprostone is an analogue of prostaglandin E2 (PGE2) that has oxytocic activity in assays of rat kidney cells and tissues. [1] There are four known receptors which mediate various but often different cellular and tissue responses to PGE2: prostaglandin EP1 receptor, prostaglandin EP2 receptor, prostaglandin EP3 receptor, and prostaglandin EP4 receptor. Sulprosotone binds to and activates the prostaglandin EP3 receptor with far greater efficacy than the other PGE2 receptors and also has the advantage of being relatively resistant, compared with PGE2, to becoming metabolically degraded. It is listed as a comparatively weak receptor agonist of the prostaglandin EP1 receptor. In all events, this as well as other potent synthetic EP3 receptor antagonists have the realized or potential ability to promote the beneficial effects of prostaglandin EP3 receptor activation. [2]

Sulprostone (as well as other prostanoids receptor agonists) is in use for inducing medical abortion and ending pregnancy after fetal death, [3] for the treatment of severe atonic postpartum hemorrhage after vaginal delivery, [4] and for removal of the placenta in patients with retained placenta. [5] Currently, sulprostone along with SC-46275, MB-28767, ONO-AE-248 and other EP3 receptor agonists are in development as drugs for the possible treatment of stomach ulcers in humans. [6]

Related Research Articles

<span class="mw-page-title-main">Prostaglandin</span> Group of physiologically active lipid compounds

Prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids that have diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derived enzymatically from the fatty acid arachidonic acid. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring. They are a subclass of eicosanoids and of the prostanoid class of fatty acid derivatives.

<span class="mw-page-title-main">Misoprostol</span> Medication to induce abortion and treat ulcers

Misoprostol is a synthetic prostaglandin medication used to prevent and treat stomach and duodenal ulcers, induce labor, cause an abortion, and treat postpartum bleeding due to poor contraction of the uterus. It is taken by mouth when used to prevent gastric ulcers in people taking nonsteroidal anti-inflammatory drugs (NSAID). For abortions it is used by itself or in conjunction with mifepristone or methotrexate. By itself, effectiveness for abortion is between 66% and 90%. For labor induction or abortion, it is taken by mouth, dissolved in the mouth, or placed in the vagina. For postpartum bleeding it may also be used rectally.

<span class="mw-page-title-main">Ductus arteriosus</span> Blood vessel connecting the pulmonary artery to the proximal descending aorta

The ductus arteriosus, also called the ductus Botalli, named after the Italian physiologist Leonardo Botallo, is a blood vessel in the developing fetus connecting the trunk of the pulmonary artery to the proximal descending aorta. It allows most of the blood from the right ventricle to bypass the fetus's fluid-filled non-functioning lungs. Upon closure at birth, it becomes the ligamentum arteriosum.

<span class="mw-page-title-main">Placenta praevia</span> Medical condition

Placenta praevia is when the placenta attaches inside the uterus but in a position near or over the cervical opening. Symptoms include vaginal bleeding in the second half of pregnancy. The bleeding is bright red and tends not to be associated with pain. Complications may include placenta accreta, dangerously low blood pressure, or bleeding after delivery. Complications for the baby may include fetal growth restriction.

<span class="mw-page-title-main">Placental abruption</span> Medical condition

Placental abruption is when the placenta separates early from the uterus, in other words separates before childbirth. It occurs most commonly around 25 weeks of pregnancy. Symptoms may include vaginal bleeding, lower abdominal pain, and dangerously low blood pressure. Complications for the mother can include disseminated intravascular coagulopathy and kidney failure. Complications for the baby can include fetal distress, low birthweight, preterm delivery, and stillbirth.

Prostaglandin E<sub>2</sub> Chemical compound

Prostaglandin E2 (PGE2), also known as dinoprostone, is a naturally occurring prostaglandin with oxytocic properties that is used as a medication. Dinoprostone is used in labor induction, bleeding after delivery, termination of pregnancy, and in newborn babies to keep the ductus arteriosus open. In babies it is used in those with congenital heart defects until surgery can be carried out. It is also used to manage gestational trophoblastic disease. It may be used within the vagina or by injection into a vein.

<span class="mw-page-title-main">Uterine atony</span> Loss of tone in the uterine musculature

Uterine atony is the failure of the uterus to contract adequately following delivery. Contraction of the uterine muscles during labor compresses the blood vessels and slows flow, which helps prevent hemorrhage and facilitates coagulation. Therefore, a lack of uterine muscle contraction can lead to an acute hemorrhage, as the vasculature is not being sufficiently compressed. Uterine atony is the most common cause of postpartum hemorrhage, which is an emergency and potential cause of fatality. Across the globe, postpartum hemorrhage is among the top five causes of maternal death. Recognition of the warning signs of uterine atony in the setting of extensive postpartum bleeding should initiate interventions aimed at regaining stable uterine contraction.

<span class="mw-page-title-main">Enprostil</span> Chemical compound

Enprostil is a synthetic prostaglandin designed to resemble dinoprostone. Enprostil was found to be a highly potent inhibitor of gastric HCl secretion. It is an analog of prostaglandin E2 but unlike this prostaglandin, which binds to and activates all four cellular receptors viz., EP1, EP2, EP3, and EP4 receptors, enprostil is a more selective receptor agonist in that it binds to and activates primarily the EP3 receptor. Consequently, enprostil is expected to have a narrower range of actions that may avoid some of the unwanted side-effects and toxicities of prostaglandin E2. A prospective multicenter randomized controlled trial conducted in Japan found combining enprostil with cimetidine was more effective than cimetidine alone in treating gastric ulcer.

<span class="mw-page-title-main">Postpartum bleeding</span> Loss of blood following childbirth

Postpartum bleeding or postpartum hemorrhage (PPH) is often defined as the loss of more than 500 ml or 1,000 ml of blood following childbirth. Some have added the requirement that there also be signs or symptoms of low blood volume for the condition to exist. Signs and symptoms may initially include: an increased heart rate, feeling faint upon standing, and an increased breathing rate. As more blood is lost, the patient may feel cold, blood pressure may drop, and they may become restless or unconscious. In severe cases circulatory collapse, disseminated intravascular coagulation and death can occur. The condition can occur up to twelve weeks following delivery in the secondary form. The most common cause is poor contraction of the uterus following childbirth. Not all of the placenta being delivered, a tear of the uterus, or poor blood clotting are other possible causes. It occurs more commonly in those who already have a low amount of red blood, are Asian, have a larger fetus or more than one fetus, are obese or are older than 40 years of age. It also occurs more commonly following caesarean sections, those in whom medications are used to start labor, those requiring the use of a vacuum or forceps, and those who have an episiotomy.

<span class="mw-page-title-main">Amniotic fluid embolism</span> Potentially fatal complication of pregnancy

An amniotic fluid embolism (AFE) is a life-threatening childbirth (obstetric) emergency in which amniotic fluid enters the blood stream of the mother, triggering a serious reaction which results in cardiorespiratory collapse and massive bleeding (coagulopathy). The rate at which it occurs is 1 instance per 20,000 births and it comprises 10% of all maternal deaths.

Most of the eicosanoid receptors are integral membrane protein G protein-coupled receptors (GPCRs) that bind and respond to eicosanoid signaling molecules. Eicosanoids are rapidly metabolized to inactive products and therefore are short-lived. Accordingly, the eicosanoid-receptor interaction is typically limited to a local interaction: cells, upon stimulation, metabolize arachidonic acid to an eicosanoid which then binds cognate receptors on either its parent cell or on nearby cells to trigger functional responses within a restricted tissue area, e.g. an inflammatory response to an invading pathogen. In some cases, however, the synthesized eicosanoid travels through the blood to trigger systemic or coordinated tissue responses, e.g. prostaglandin (PG) E2 released locally travels to the hypothalamus to trigger a febrile reaction. An example of a non-GPCR receptor that binds many eicosanoids is the PPAR-γ nuclear receptor.

Prostaglandin EP<sub>4</sub> receptor Protein-coding gene in the species Homo sapiens

Prostaglandin E2 receptor 4 (EP4) is a prostaglandin receptor for prostaglandin E2 (PGE2) encoded by the PTGER4 gene in humans; it is one of four identified EP receptors, the others being EP1, EP2, and EP3, all of which bind with and mediate cellular responses to PGE2 and also, but generally with lesser affinity and responsiveness, certain other prostanoids (see Prostaglandin receptors). EP4 has been implicated in various physiological and pathological responses in animal models and humans.

Prostaglandin EP<sub>1</sub> receptor Protein-coding gene in the species Homo sapiens

Prostaglandin E2 receptor 1 (EP1) is a 42kDa prostaglandin receptor encoded by the PTGER1 gene. EP1 is one of four identified EP receptors, EP1, EP2, EP3, and EP4 which bind with and mediate cellular responses principally to prostaglandin E2) (PGE2) and also but generally with lesser affinity and responsiveness to certain other prostanoids (see Prostaglandin receptors). Animal model studies have implicated EP1 in various physiological and pathological responses. However, key differences in the distribution of EP1 between these test animals and humans as well as other complicating issues make it difficult to establish the function(s) of this receptor in human health and disease.

Prostaglandin EP<sub>2</sub> receptor Protein-coding gene in the species Homo sapiens

Prostaglandin E2 receptor 2, also known as EP2, is a prostaglandin receptor for prostaglandin E2 (PGE2) encoded by the human gene PTGER2: it is one of four identified EP receptors, the others being EP1, EP3, and EP4, which bind with and mediate cellular responses to PGE2 and also, but with lesser affinity and responsiveness, certain other prostanoids (see Prostaglandin receptors). EP has been implicated in various physiological and pathological responses.

Prostaglandin EP<sub>3</sub> receptor Protein-coding gene in the species Homo sapiens

Prostaglandin EP3 receptor (EP3, 53kDa), is a prostaglandin receptor for prostaglandin E2 (PGE2) encoded by the human gene PTGER3; it is one of four identified EP receptors, the others being EP1, EP2, and EP4, all of which bind with and mediate cellular responses to PGE2 and also, but generally with lesser affinity and responsiveness, certain other prostanoids (see Prostaglandin receptors). EP has been implicated in various physiological and pathological responses.

<span class="mw-page-title-main">Prostaglandin F receptor</span> Protein-coding gene in the species Homo sapiens

Prostaglandin F receptor (FP) is a receptor belonging to the prostaglandin (PG) group of receptors. FP binds to and mediates the biological actions of prostaglandin F (PGF). It is encoded in humans by the PTGFR gene.

<span class="mw-page-title-main">MPGES-1</span> Protein-coding gene in the species Homo sapiens

Microsomal prostaglandin E synthase-1 (mPGES-1) or Prostaglandin E synthase is an enzyme that in humans is encoded by the PTGES gene.

A uterotonic, also known as an oxytocic or ecbolic, is a type of medication used to induce contraction or greater tonicity of the uterus. Uterotonics are used both to induce labor and to reduce postpartum hemorrhage.

<span class="mw-page-title-main">Placental expulsion</span> Ejection of the placenta from the uterus after childbirth

Placental expulsion occurs when the placenta comes out of the birth canal after childbirth. The period from just after the baby is expelled until just after the placenta is expelled is called the third stage of labor.

The prostaglandin E2 (PGE2) receptors are G protein-coupled receptors that bind and are activated by prostaglandin E2. They are members of the prostaglandin receptors class of receptors and include the following Protein isoforms:

References

  1. Tamma G, Wiesner B, Furkert J, et al. (August 2003). "The prostaglandin E2 analogue sulprostone antagonizes vasopressin-induced antidiuresis through activation of Rho". Journal of Cell Science. 116 (Pt 16): 3285–94. doi: 10.1242/jcs.00640 . hdl:11586/43242. PMID   12829746.
  2. Moreno JJ (2017). "Eicosanoid receptors: Targets for the treatment of disrupted intestinal epithelial homeostasis". European Journal of Pharmacology. 796: 7–19. doi:10.1016/j.ejphar.2016.12.004. PMID   27940058. S2CID   1513449.
  3. Van Mensel K, Claerhout F, Debois P, Keirse MJ, Hanssens M (2009). "A randomized controlled trial of misoprostol and sulprostone to end pregnancy after fetal death". Obstetrics and Gynecology International. 2009: 496320. doi: 10.1155/2009/496320 . PMC   2778817 . PMID   19960062.
  4. Schmitz T, Tararbit K, Dupont C, Rudigoz RC, Bouvier-Colle MH, Deneux-Tharaux C (2011). "Prostaglandin E2 analogue sulprostone for treatment of atonic postpartum hemorrhage". Obstetrics and Gynecology. 118 (2 Pt 1): 257–65. doi:10.1097/AOG.0b013e3182255335. PMID   21775840. S2CID   11989341.
  5. Grillo-Ardila CF, Ruiz-Parra AI, Gaitán HG, Rodriguez-Malagon N (2014). "Prostaglandins for management of retained placenta". The Cochrane Database of Systematic Reviews (5): CD010312. doi: 10.1002/14651858.CD010312.pub2 . PMC   11055606 . PMID   24833288.
  6. Markovič T, Jakopin Ž, Dolenc MS, Mlinarič-Raščan I (2017). "Structural features of subtype-selective EP receptor modulators". Drug Discovery Today. 22 (1): 57–71. doi: 10.1016/j.drudis.2016.08.003 . PMID   27506873.