Prostaglandin E2

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Prostaglandin E2
Prostaglandin E2.svg
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Clinical data
Trade names Prostin E2, Cervidil, Propess, others
Other namesPGE2, (5Z,11α,13E,15S)-11,15-Dihydroxy-9-oxo-prosta-5,13-dien-1-oic acid
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MedlinePlus a682512
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administration 		Intravaginal, IV
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Legal status
Identifiers
  • (5Z,11α,13E,15S)-7-[3-hydroxy-2-(3-hydroxyoct-1-enyl)- 5-oxo-cyclopentyl] hept-5-enoic acid
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Chemical and physical data
Formula C20H32O5
Molar mass 352.471 g·mol−1
3D model (JSmol)
  • CCCCC[C@@H](/C=C/[C@H]1[C@@H](CC(=O)[C@@H]1C/C=C\CCCC(=O)O)O)O
  • InChI=1S/C20H32O5/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/h4,7,12-13,15-17,19,21,23H,2-3,5-6,8-11,14H2,1H3,(H,24,25)/b7-4-,13-12+/t15-,16+,17+,19+/m0/s1 X mark.svgN
  • Key:XEYBRNLFEZDVAW-ARSRFYASSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Prostaglandin E2 (PGE2), also known as dinoprostone, is a naturally occurring prostaglandin with oxytocic properties that is used as a medication. [2] [3] [4] Dinoprostone is used in labor induction, bleeding after delivery, termination of pregnancy, and in newborn babies to keep the ductus arteriosus open. [2] [5] In babies it is used in those with congenital heart defects until surgery can be carried out. [5] It is also used to manage gestational trophoblastic disease. [4] It may be used within the vagina or by injection into a vein. [2] [6]

Contents

PGE2 synthesis within the body begins with the activation of arachidonic acid (AA) by the enzyme phospholipase A2. Once activated, AA is oxygenated by cyclooxygenase (COX) enzymes to form prostaglandin endoperoxides. Specifically, prostaglandin G2 (PGG2) is modified by the peroxidase moiety of the COX enzyme to produce prostaglandin H2 (PGH2) which is then converted to PGE2. [7] [8]

Common side effects of PGE2 include nausea, vomiting, diarrhea, fever, and excessive uterine contraction. [2] In babies there may be decreased breathing and low blood pressure. [5] Caution should be taken in people with asthma or glaucoma and it is not recommended in those who have had a prior C-section. [9] It works by binding and activating the prostaglandin E2 receptor which results in the opening and softening of the cervix and dilation of blood vessels. [2] [5]

Prostaglandin E2 was first synthesized in 1970 and approved for medical use by the FDA in the United States in 1977. [5] [2] It is on the World Health Organization's List of Essential Medicines. [10] Prostaglandin E2 works as well as prostaglandin E1 in babies. [5]

Physiological effects

Dinoprostone has important effects in labor by inducing softening of the cervix and causing uterine contraction, and also stimulates osteoblasts to release factors that stimulate bone resorption by osteoclasts. [11]

Natural prostaglandins, including PGE1 and PGE2, are important in the structure and function of the ductus arteriosus in fetuses and newborns. [12] They allow the ductus arteriosus to remain open, providing the necessary connection between the pulmonary artery and descending aorta that allows the blood to bypass the fetus's underdeveloped lungs and be transported to the placenta for oxygenation. [12] The ductus arteriosus normally begins to close upon birth due to an increase of PGE2 metabolism, but in newborns with congenital heart disease, prostaglandins can be used to keep the ductus arteriosus open longer than normal to sustain healthy oxygen saturation levels in the blood. [7] [12] Although PGE1 is more commonly used in this setting, there has been a report of oral PGE2 being used to treat ductus-dependent congenital heart diseases in newborns to delay surgical treatment until the pulmonary arteries grew. [13] In addition, PGE2 was used in another report to dilate the ductus arteriosus in newborns with various cardiovascular defects to allow for better perfusion of the lungs and kidneys. [14] On the other hand, the post-partal synthesis of PGE2 in newborns is considered one cause of patent ductus arteriosus. [15]

When administered in aerosol form, PGE2 serves as a bronchodilator, but its use in this setting is limited by the fact that it also causes coughing. [7]

PGE2, similarly to PGE1, acts as a direct vasodilator by acting on smooth muscle to cause dilation of blood vessels. [7] In addition, PGE2 inhibits platelet aggregation. [7]

PGE2 also suppresses T cell receptor signaling and proliferation, and may play a role in resolution of inflammation. [7] [16] In addition, PGE2 limits the immune response by preventing B-lymphocyte differentiation and their ability to present antigens. [7]

Central and peripheral nervous systems effects

Prostaglandin E2 (PGE2) has a variety of functions within the central nervous system and peripheral nervous system. When PGE2 interacts with EP3 receptors, it increases body temperature, resulting in fever. [7] PGE2 is also a predominant prostanoid that contributes to inflammation via enhancing edema and leukocyte infiltration from increased vascular permeability (allowing more blood flow into an inflamed area of the body) when acting on EP2 receptors. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) blocks the activity of COX-2, resulting in a decrease of PGE2 production. NSAIDs blocking COX-2 and decreasing the production of PGE2 remediates fever and inflammation. [7] [17]

Additionally, PGE2 acting on EP1 and EP4 receptors are a component in feeling pain via inflammatory nociception. [18] When PGE2 binds to EP1 and EP4 receptors, an increase in excitability via cation channels as well as inhibition of hyperpolarizing potassium (K+) channels, increase membrane excitability. As a result, this causes peripheral nerve endings to report painful stimuli. [7]

Immunity

As mentioned previously, prostaglandin E2 (PGE2) contributes to the inflammation when bound to EP2 receptors. In terms of immunity, prostaglandins have the ability to regulate lymphocyte function. PGE2 affects T-lymphocyte formation by regulating apoptosis of immature thymocytes. In addition, it can suppress an immune response by inhibiting B lymphocytes from forming into antibody-secreting plasma cells. When this process is suppressed, it causes a decrease in a humoral antibody response because of the decrease in production of antibodies. PGE2 also has roles in inhibition of cytotoxic T-cell function, cell division of T-lymphocytes, and the development of TH1 lymphocytes. [7] [19]

Neurological effects

In response to physiologic and psychologic stress, prostaglandin E2 (PGE2) is involved in several inflammation and immunity pathways. As one of the most abundant prostaglandins in the body, PGE2 is involved almost all typical inflammation markers such as redness, swelling, and pain. [20] It regulates these responses through binding to G coupled protein prostaglandin E2 receptors (EP1, EP2, EP3, and EP4). The activation of these different EP receptors is dependent on the type of triggering stress stimuli and results in the corresponding stress response. Activation of EP1 via PGE2 results in the suppression of impulse behaviors in response to psychological stress. PGE2 is involved in regulating illness-induced memory impairment via activation of EP2. PGE2 activation of EP3 results in regulation of illness induced fever. EP4 is functionally similar to EP2 and has also been shown in studies to have a role in hypothermia and anorexia. [21] In addition to inflammatory effects, PGE2 has been shown to have anti-inflammatory effects as well, due to its different actions on varying receptors. [20]

Smooth muscle effects

Prostaglandin E2 (PGE2) serves a significant role in vascular smooth muscle tone regulation. It is a vasodilator produced by endothelial cells. It promotes vasodilation of smooth muscles by increasing the activity of cyclic adenosine monophosphate (cAMP) to decrease intracellular calcium levels via the IP and EP4 receptors. [7] Conversely, PGE2 can also induce vasoconstriction via activation of EP1 and EP3 receptors, which activates the Ca2+ pathway and decreased cAMP activity. [22]

Within the gastrointestinal tract, PGE2 activates smooth muscles to cause contractions on longitudinal muscle when acting on EP3 receptors. In contrast, PGE2 effects on respiratory smooth muscle result in relaxation. [23]

Kidney effects

Prostaglandin E2 (PGE2), along with other prostaglandins, are synthesized within the cortex and medulla of the kidney. The role of renal COX-2-derived PGE2 within the kidney is to maintain renal blood flow and glomerular filtration rate (GFR) through localized vasodilation. COX-2-derived prostanoids work to increase medullary blood flow as well as inhibit sodium reabsorption within kidney tubules. PGE2 also assists the kidneys with systemic blood pressure control by modifying water and sodium excretion. In addition, it is also thought to activate EP4 or EP2 to increase renin release, resulting in an elevation of GFR and sodium retention to raise systemic blood pressure levels within the body. [7]

Medical uses

Cervical ripening

In the setting of labor and delivery, cervical ripening (also known as cervical effacement) is a natural process that occurs before labor, in which the cervix becomes softer, thinner, and dilated, enabling the fetus to pass through the cervix. [3] A ripe cervix is favorable prior to induction of labor, which is a common obstetric practice, and increases the chances for a successful induction. [24] Pharmacological methods are sometimes required to induce cervical ripening that does not occur naturally. [25] The natural ripening of the cervix is mediated by prostaglandins, thus a common pharmacological method is to use external prostaglandins such as PGE2, or dinoprostone. [3] Results of a systematic review and meta-analysis of the literature found that outpatient cervical ripening with dinoprostone or single-balloon catheters did not increase the risk of cesarean deliveries. [26] [27]

Prostaglandin E2 (PGE2) achieves cervical ripening and softening by stimulating uterine contractions as well as directly acting on the collagenase present in the cervix to soften it. [7] There are currently two formulations of PGE2 analog available for use in cervical ripening: Prepidil, a vaginal gel, and Cervidil, a vaginal insert. [24] PGE2 is similar to oxytocin in terms of successful labor induction and the time from induction to delivery. [7]

Termination of intrauterine pregnancy

PGE2 is a common pharmacological method of termination of pregnancy, particularly in the second trimester or for missed abortion, which is a miscarriage in which the fetus did not evacuate the uterus. [7] [28] [29] However, PGE2 is not feticidal, and only induces abortion by stimulating uterine contractions. [4] It is recommended that 20 mg of dinoprostone vaginal suppository be administered every three to five hours to evacuate the uterus. [7] [4] The abortion should occur within 24 hours after the beginning of administration of dinoprostone; if it does not, dinoprostone should no longer be given and other interventions would be required, such as dilation and curettage. [7] [4]

Side effects

A common side effect of prostaglandin E2 is its effect on gastrointestinal smooth muscle resulting in nausea, vomiting and diarrhea. Other side effects include headache, shivering, and chills. [4] The suppository form of prostaglandin E2 is associated with increased severity of these symptoms. Fever is also a common side effect with use of prostaglandin E2. Administration of prostaglandin E2 should be stopped if a person experiences side effects such as fever. [4]

The insert and gel forms have been shown to have minimal gastrointestinal effects, but are more associated with increase stimulation of the uterus as well as fetal distress. [4] Uterine hyperstimulation is effectively treated by stopping use of prostaglandin E2. [4] Other monitoring parameters include sustained uterine contractions and fetal distress. [4] In babies there may be decreased breathing and low blood pressure. [5] Care should be taken in people with asthma or glaucoma and it is not recommended in those who have had a prior C-section. [9]

Mechanism of action

Prostaglandin E2 (PGE2) binds to G protein-coupled receptors (GPCRs) EP1, EP2, EP3, and EP4 to cause various downstream effects to cause direct contractions in the myometrium. [4] In addition, PGE2 inhibits Na+ absorption within the Thick Ascending Limb (TAL) of the Loop of Henle and ADH-mediated water transport in collecting tubules. As a result, blockage of PGE2 synthesis with NSAIDs can limit the efficacy of loop diuretics. [4]

Administration

Prostaglandin E2 (PGE2) should only be administered by, or under the direct supervision of, a physician and careful monitoring should be performed. [4] PGE2 comes in many dosage forms with varying pharmacokinetic properties. For example PGE2 can come in a gel formulation that requires six hour dosing or it can come as a slow release dinoprostone pessary that does not need to be re-administered and can be taken out if necessary. [30] In a quality improvement project done in UK, the switch from prostaglandin gel to the slow release dinoprostone pessary was able to lower cesarian section rates in women undergoing induction of labor in maternity care. [30]

For the vaginal insert (brand name Cervidil), the manufacturer recommends keeping the medication frozen until use since it does not need to be warmed to room temperature. [31] Once the package is open, a water miscible lubricant may be used to insert the medication, using your finger place the device into the vagina and position the device transversely in the posterior vaginal fornix. [31] The person receiving the drug should remain laying down for two hours after administration of the insert is complete. [31] The manufacturer also recommends waiting 30 minutes after removal of insert before starting oxytocin. [31]

The vaginal gel (brand name Prostin E2, Canada) is administered through a prefilled syringe and the medication is placed in the posterior fornix of the vagina. After administration people should stay laying down for at least 30 minutes after they have received the drug. [32]

Contraindications

Contraindications to a medication are any reasons to not use the drug. Prostaglandin E2 (PGE2) is used to induce labor and should not be used in people that are contraindicated to give birth vaginally or spontaneous labor. [25] PGE2 should not be used in people with allergies to prostaglandins or any components in the drugs formulations. [4] PGE2 should be stopped before other oxytocic agents like oxytocin are given. [4]

Dinoprostone as a vaginal suppository is contraindicated for women with acute pelvic inflammatory disease or active disease of the cardiovascular, respiratory, hepatic, or renal systems. Caution is required for people with a history of cervical malignancy, hypo- or hypertension, anemia, epilepsy, jaundice, asthma, or pulmonary diseases. The suppository formulation is also not indicated for viable fetus evacuation. [4]

Endocervical gel is contraindicated in those with who have a history of C-sections or major uterine surgery, if the fetus is in distress and delivery is not imminent, vaginal bleeding throughout the pregnancy that is unexplained, history of difficult labors and deliveries, have cephalopelvic disproportion, less than six previous term babies with nonvertex presentation, hyper or hypotonic uterine patterns. [4]

Toxicity

When prostaglandin E2 (PGE2) is given in excess, hyper-stimulation of the uterus occurs and immediate discontinuation of the drug usually results in resolution of toxic effects. [33] [4] If symptoms continue a beta adrenergic drug (e.g. terbutaline) can be used.[ citation needed ]

There are many different dosage forms of PGE2. The pharmacokinetic properties vary between dosage forms and should not be interchanged. A medication error was cited in the Institute for Safe Medication Practices where Prostin E2 was used in place of Cervidil. The hospital had run out of Cervidil which is a 10 mg endocervical insert and the provider decided to use half of a 20 mg Prostin E2 vaginal suppository. Cervidil delivers the drug at a constant rate and can be removed as necessary while Prostin E2 dissolves immediately and can not be removed. This error resulted in an emergency C-section since the fetus's heart rate dropped suddenly. [34]

Pharmacokinetics

The synthetic PGE2 dinoprostone has a plasma half-life of approximately 2.5–5 minutes, after vaginal administration, with most metabolites being excreted in the urine. [7]

History

Swedish physiologist Ulf von Euler and British physiologist M.W. Goldblatt, first discovered prostaglandins independently in 1935 as factors contained in human seminal fluid. [35] Prostaglandins were noted for having blood pressure reducing effects and smooth muscle regulation effects. [36] Prostaglandin E2 itself was identified in 1962 by Swedish biochemist Sune Bergström in the seminal fluid of sheep. [35] The structure of prostaglandins is conserved in mammals, but it is also produced by marine organisms which allowed for more research into their biological roles. [36] Prostaglandins were discovered to be products of arachidonic acid and with the ability to radio label arachidonic acid in the early 1960s, American chemist E.J. Corey was able to synthesize prostaglandin E2 in the lab in the 1970. [36] This advancement paved the way for later studies that helped define the actions and response of prostaglandin E2. Prostaglandin E2 was approved for medical use in the United States in 1977 and it is on the World Health Organization's List of Essential Medicines. [2] [10] Prostaglandin E2 was approved by the FDA in 1977. [37]

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.

Labor induction is the process or treatment that stimulates childbirth and delivery. Inducing (starting) labor can be accomplished with pharmaceutical or non-pharmaceutical methods. In Western countries, it is estimated that one-quarter of pregnant women have their labor medically induced with drug treatment. Inductions are most often performed either with prostaglandin drug treatment alone, or with a combination of prostaglandin and intravenous oxytocin treatment.

Bishop score, also Bishop's score or cervix score, is a pre-labor scoring system to assist in predicting whether induction of labor will be required. It has also been used to assess the likelihood of spontaneous preterm delivery. The Bishop score was developed by Professor Emeritus of Obstetrics and Gynecology, Edward Bishop, and was first published in August 1964.

Cervical dilation is the opening of the cervix, the entrance to the uterus, during childbirth, miscarriage, induced abortion, or gynecological surgery. Cervical dilation may occur naturally, or may be induced surgically or medically.

Bloody show or show is the passage of a small amount of blood or blood-tinged mucus through the vagina near the end of pregnancy. It is caused by thinning and dilation of the cervix, leading to detachment of the cervical mucus plug that seals the cervix during pregnancy and tearing of small cervical blood vessels, and is one of the signs that labor may be imminent. The bloody show may be expelled from the vagina in pieces or altogether and often appears as a jelly-like piece of mucus stained with blood. Although the bloody show may be alarming at first, it is not a concern of patient health after 37 weeks gestation.

<span class="mw-page-title-main">Cervical effacement</span> Thinning and shortening of the cervix

Cervical effacement or cervical ripening refers to the thinning and shortening of the cervix. This process occurs during labor to prepare the cervix for dilation to allow the fetus to pass through the vagina. While this is a normal, physiological process that occurs at the later end of pregnancy, it can also be induced through medications and procedures.

<span class="mw-page-title-main">Iloprost</span> Pharmaceutical drug

Iloprost, sold under the brand name Ventavis among others, is a medication used to treat pulmonary arterial hypertension (PAH), scleroderma, Raynaud's phenomenon, frostbite, and other conditions in which the blood vessels are constricted and blood cannot flow to the tissues. Iloprost is a prostacyclin mimetic.

<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.

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.

<span class="mw-page-title-main">Osmotic dilator</span> Medical device to dilate the uterine cervix

Osmotic dilators, also known as hygroscopic dilators, are medical implements used to dilate the uterine cervix by swelling as they absorb fluid from surrounding tissue. They may be composed of natural or synthetic materials. A laminaria stick or tent is a thin rod made of the stems of dried Laminaria, a genus of kelp. Laminaria sticks can be generated from Laminaria japonica and Laminaria digitata. Synthetic osmotic dilators are commonly referred to by their brand names, such as Dilapan. Dilapan-S are composed of polyacrylonitrile, a plastic polymer. The hygroscopic nature of the polymer causes the dilator to absorb fluid and expand.

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">Sulprostone</span> Chemical compound

Sulprostone is an analogue of prostaglandin E2 (PGE2) that has oxytocic activity in assays of rat kidney cells and tissues. 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.

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.

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:

<span class="mw-page-title-main">Grapiprant</span> NSAID anti-inflammatory veterinary drug

Grapiprant, sold under the brand name Galliprant, is a small molecule drug that belongs in the piprant class. This analgesic and anti-inflammatory drug is primarily used as a pain relief for mild to moderate inflammation related to osteoarthritis in dogs. Grapiprant has been approved by the FDA's Center for Veterinary Medicine and was categorized as a non-cyclooxygenase inhibiting non-steroidal anti-inflammatory drug (NSAID) in March 2016.

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