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 inducting 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 having 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.

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

Chorioamnionitis, also known as intra-amniotic infection (IAI), is inflammation of the fetal membranes, usually due to bacterial infection. In 2015, a National Institute of Child Health and Human Development Workshop expert panel recommended use of the term "triple I" to address the heterogeneity of this disorder. The term triple I refers to intrauterine infection or inflammation or both and is defined by strict diagnostic criteria, but this terminology has not been commonly adopted although the criteria are used.

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">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. The condition can occur up to six weeks following delivery.

Placental insufficiency or utero-placental insufficiency is the failure of the placenta to deliver sufficient nutrients to the fetus during pregnancy, and is often a result of insufficient blood flow to the placenta. The term is also sometimes used to designate late decelerations of fetal heart rate as measured by cardiotocography or an NST, even if there is no other evidence of reduced blood flow to the placenta, normal uterine blood flow rate being 600mL/min.

<span class="mw-page-title-main">Carbetocin</span> Pabal contains carbetocin used for preventing postpartum bleeding. Potent than oxytocin.

Carbetocin, sold under the brand names Pabal among others, is a medication used to prevent excessive bleeding after childbirth, particularly following Cesarean section. It appears to work as well as oxytocin. Due to it being less economical than other options, use is not recommended by NHS Scotland. It is given by injection into a vein or muscle.

<span class="mw-page-title-main">Vaginal delivery</span> Delivery through the vagina

A vaginal delivery is the birth of offspring in mammals through the vagina. It is the most common method of childbirth worldwide. It is considered the preferred method of delivery, with lower morbidity and mortality than Caesarean sections (C-sections).

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 (53kDa), also known as EP3, 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.

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>

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.

Anemia is a condition in which blood has a lower-than-normal amount of red blood cells or hemoglobin. Anemia in pregnancy is a decrease in the total red blood cells (RBCs) or hemoglobin in the blood during pregnancy. Anemia is an extremely common condition in pregnancy world-wide, conferring a number of health risks to mother and child. While anemia in pregnancy may be pathologic, in normal pregnancies, the increase in RBC mass is smaller than the increase in plasma volume, leading to a mild decrease in hemoglobin concentration referred to as physiologic anemia. Maternal signs and symptoms are usually non-specific, but can include: fatigue, pallor, dyspnea, palpitations, and dizziness. There are numerous well-known maternal consequences of anemia including: maternal cardiovascular strain, reduced physical and mental performance, reduced peripartum blood reserves, increased risk for peripartum blood product transfusion, and increased risk for maternal mortality.

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. 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.