DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/11274341Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/24141993
http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/018261s031lbl.pdf
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11274341
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/24141993
http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/018261s031lbl.pdf
More than a century ago, Sir Henry Dale demonstrated that a component of the pituitary causes contractions of the mammalian uterus, hence his coining the term “oxytocic,” derived from the Greek for “quick birth,” for its activity. The discovery that a component of the pituitary causes milk secretion followed within a few years. By 1930, oxytocin was separated from vasopressin into pitocin and pitressin, respectively, at Parke Davis and made available for research. That a single peptide was responsible for these uterine and mammary actions was definitively confirmed upon the sequencing and synthesis of the peptide, 9 amino acids in length. Vincent du Vigneaud was awarded a Nobel Prize for this work.
Oxytocin is indicated for the initiation or improvement of uterine contractions, where this is desirable and considered suitable for reasons of fetal or maternal concern, in order to achieve vaginal delivery. Oxytocin is indicated to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage. Uterine motility depends on the formation of the contractile protein actomyosin under the influence of the Ca2+- dependent phosphorylating enzyme myosin light-chain kinase. Oxytocin promotes contractions by increasing the intracellular Ca2+. Oxytocin has specific receptors in the myometrium and the receptor concentration increases greatly during pregnancy, reaching a maximum in early labor at term. The Oxytocin receptor is a typical class I G protein-coupled receptor that is primarily coupled via G(q) proteins to phospholipase C-beta. The high-affinity receptor state requires both Mg(2+) and cholesterol, which probably function as allosteric modulators. The agonist-binding region of the receptor has been characterized by mutagenesis and molecular modeling and is different from the antagonist binding site. The function and physiological regulation of the Oxytocin system is strongly steroid dependent.
CNS Activity
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16994116/ | https://www.ncbi.nlm.nih.gov/pubmed/13305558/
Curator's Comment: references retrieved from | https://www.ncbi.nlm.nih.gov/pubmed/24141993
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2049 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11274341 |
0.76 nM [Kd] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Preventing | PITOCIN Approved UsePitocin® (Oxytocin Injection, USP) Synthetic is indicated Antepartum and Postpartum. Antepartum: Pitocin is indicated for the initiation or improvement of uterine contractions, where this is desirable and considered suitable for reasons of fetal or maternal concern, in order to achieve vaginal delivery. It is indicated for (1) induction of labor in patients with a medical indication for the initiation of labor, such as Rh problems, maternal diabetes, preeclampsia at or near term, when delivery is in the best interests of mother and fetus or when membranes are prematurely ruptured and delivery is indicated; (2) stimulation or reinforcement of labor, as in selected cases of uterine inertia; (3) as adjunctive therapy in the management of incomplete or inevitable abortion. In the first trimester, curettage is generally considered primary therapy. In second trimester abortion, oxytocin infusion will often be successful in emptying the uterus. Other means of therapy, however, may be required in such cases. Postpartum: Pitocin is indicated to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage. Launch Date1981 |
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| Primary | PITOCIN Approved UsePitocin® (Oxytocin Injection, USP) Synthetic is indicated Antepartum and Postpartum. Antepartum: Pitocin is indicated for the initiation or improvement of uterine contractions, where this is desirable and considered suitable for reasons of fetal or maternal concern, in order to achieve vaginal delivery. It is indicated for (1) induction of labor in patients with a medical indication for the initiation of labor, such as Rh problems, maternal diabetes, preeclampsia at or near term, when delivery is in the best interests of mother and fetus or when membranes are prematurely ruptured and delivery is indicated; (2) stimulation or reinforcement of labor, as in selected cases of uterine inertia; (3) as adjunctive therapy in the management of incomplete or inevitable abortion. In the first trimester, curettage is generally considered primary therapy. In second trimester abortion, oxytocin infusion will often be successful in emptying the uterus. Other means of therapy, however, may be required in such cases. Postpartum: Pitocin is indicated to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage. Launch Date1981 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Oxytocin decreases methamphetamine self-administration, methamphetamine hyperactivity, and relapse to methamphetamine-seeking behaviour in rats. | 2010-01 |
|
| The effect of ovarian steroids on oxytocin-stimulated secretion and synthesis of prostaglandins in bovine myometrial cells. | 2009-12 |
|
| Trends in postpartum hemorrhage in high resource countries: a review and recommendations from the International Postpartum Hemorrhage Collaborative Group. | 2009-11-27 |
|
| The role of cervical Electrical Impedance Spectroscopy in the prediction of the course and outcome of induced labour. | 2009-09-02 |
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| Involvement of the transcription factor STAT1 in the regulation of porcine ovarian granulosa cell functions treated and not treated with ghrelin. | 2009-09 |
|
| Study protocol. ECSSIT - Elective Caesarean Section Syntocinon Infusion Trial. A multi-centre randomised controlled trial of oxytocin (Syntocinon) 5 IU bolus and placebo infusion versus oxytocin 5 IU bolus and 40 IU infusion for the control of blood loss at elective caesarean section. | 2009-08-24 |
|
| [Frequency of uterine rupture at delivery and accompanying risks for the mother and the newborn]. | 2009-08 |
|
| A randomised controlled trial comparing the efficacy of intramuscular syntometrine and intravenous syntocinon, in preventing postpartum haemorrhage. | 2009-07 |
|
| "Oxytocin hand": extravasation and vascular compromise after obstetrical pitocin. | 2009-07 |
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| Anaesthesiological considerations on tocolytic and uterotonic therapy in obstetrics. | 2009-07 |
|
| [Effectiveness of non-pharmacological strategies in relieving labor pain]. | 2009-06 |
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| External aortic compression device: the first aid for postpartum hemorrhage control. | 2009-06 |
|
| Effects of oxytocin on methamphetamine-induced conditioned place preference and the possible role of glutamatergic neurotransmission in the medial prefrontal cortex of mice in reinstatement. | 2009-04 |
|
| Using snowball sampling method with nurses to understand medication administration errors. | 2009-02 |
|
| Pulseless electrical activity during caesarean delivery under spinal anaesthesia: a case report of severe anaphylactic reaction to Syntocinon. | 2009-01 |
|
| A randomized controlled trial of misoprostol and sulprostone to end pregnancy after fetal death. | 2009 |
|
| Post partum haemorrhage secondary to uterine atony, complicated by platelet storage pool disease and partial placenta diffusa: a case report. | 2008-12-13 |
|
| [Effect of acupuncture on Cx43 knock-out mice dysmenorrhea response]. | 2008-12 |
|
| Intraumbilical veinous injection oxytocin in the active management of third stage of labour. | 2008-09 |
|
| The hemodynamics of oxytocin and other vasoactive agents during neuraxial anesthesia for cesarean delivery: findings in six cases. | 2008-07 |
|
| [Clinical and experimental study on effect of cuichan zhusheng decoction on the structure and tension of pregnant cervix uteri]. | 2008-06 |
|
| Prenatal organochlorine exposure and measures of behavior in infancy using the Neonatal Behavioral Assessment Scale (NBAS). | 2008-05 |
|
| Signs of myocardial ischaemia after injection of oxytocin: a randomized double-blind comparison of oxytocin and methylergometrine during Caesarean section. | 2008-05 |
|
| [Study on effects of acupuncture on mice dysmenorrhea model and the mechanism]. | 2008-02 |
|
| The views of obstetricians in the south-west of England on the use of prostaglandins and syntocinon in VBAC. | 2008-02 |
|
| National survey of obstetricians in Wales regarding induction of labour in women with a previous caesarean section. | 2008-01 |
|
| Predicting a failed induction. | 2007-10 |
|
| Experiences of non-progressive and augmented labour among nulliparous women: a qualitative interview study in a Grounded Theory approach. | 2007-07-28 |
|
| The influence of the timing of cord clamping on postnatal cerebral oxygenation in preterm neonates: a randomized, controlled trial. | 2007-03 |
|
| Oxytocin increases retention of social cognition in autism. | 2007-02-15 |
|
| Development and validation of a stability-indicating analytical method for the quantitation of oxytocin in pharmaceutical dosage forms. | 2007-01-04 |
|
| [Is it already time to legalize the usage of Cytotec (Misoprostol) in the obstetrics' practice?]. | 2007 |
|
| Avoiding manual removal of placenta: evaluation of intra-umbilical injection of uterotonics using the Pipingas technique for management of adherent placenta. | 2007 |
|
| Distribution of MT1 melatonin receptor immunoreactivity in the human hypothalamus and pituitary gland: colocalization of MT1 with vasopressin, oxytocin, and corticotropin-releasing hormone. | 2006-12-20 |
|
| A randomised trial of carbetocin versus syntometrine in the management of the third stage of labour. | 2006-12 |
|
| Porcine reproductive and respiratory syndrome virus (PRRSV) infection spreads by cell-to-cell transfer in cultured MARC-145 cells, is dependent on an intact cytoskeleton, and is suppressed by drug-targeting of cell permissiveness to virus infection. | 2006-11-02 |
|
| Uterine rupture during pregnancy and delivery among women attending the Al-Tthawra Hospital in Sana'a City Yemen Republic. | 2006-11 |
|
| [Effect of the calcitonine gene-related peptide on the myometrium contractile activity]. | 2006-09 |
|
| IMOP: randomised placebo controlled trial of outpatient cervical ripening with isosorbide mononitrate (IMN) prior to induction of labour - clinical trial with analyses of efficacy, cost effectiveness and acceptability. | 2006-07-25 |
|
| Therapeutic termination of second trimester pregnancies with low dose misoprostol. | 2006-07 |
|
| Using clinical audit to improve the quality of obstetric care at the Tibetan Delek Hospital in North India: a longitudinal study. | 2006-06-07 |
|
| [Delivery of a macrosomic infant: factors predictive of failed labor]. | 2006-05 |
|
| [Pharmacodynamical study on Danqi capsule]. | 2005-12 |
|
| Randomized controlled trial of vaginal misoprostol versus vaginal misoprostol and isosorbide dinitrate for termination of pregnancy at 13-29 weeks. | 2005-12 |
|
| Maternal complications with vaginal birth after cesarean delivery: a multicenter study. | 2005-11 |
|
| Selectivity of d[Cha4]AVP and SSR149415 at human vasopressin and oxytocin receptors: evidence that SSR149415 is a mixed vasopressin V1b/oxytocin receptor antagonist. | 2005-11 |
|
| Does the maxim "once a Caesarean, always a Caesarean" still hold true? | 2005-09 |
|
| [Effects of epidural ropivacaine labor analgesia on duration of labor and mode of delivery]. | 2005-06 |
|
| Ruptured uterus in a primigravida: a case report. | 2005-03 |
|
| Oxytocin attenuates the cocaine-induced exploratory hyperactivity in mice. | 1990-11-01 |
Patents
Sample Use Guides
The dosage of (Oxytocin Injection, USP) Synthetic is determined by the uterine response and must therefore be individualized and initiated at a very low level. The following dosage information is based upon various regimens and indications in general use.
A. Induction or Stimulation of Labor
Intravenous infusion (drip method) is the only acceptable method of parenteral administration of Pitocin for the induction or stimulation of labor. Accurate control of the rate of infusion is essential and is best accomplished by an infusion pump. It is convenient to piggyback the Pitocin infusion on a physiologic electrolyte solution,
permitting the Pitocin infusion to be stopped abruptly without interrupting the electrolyte infusion. This is done in the following way.
1. Preparation
a. The standard solution for infusion of Pitocin is prepared by adding the contents of one 1-mL vial containing 10 units of oxytocin to 1000 mL of 0.9% aqueous sodium chloride or Ringer's lactate. The combined solution containing 10
milliunits (mU) of oxytocin/mL is rotated in the infusion bottle for thorough mixing.
b. Establish the infusion with a separate bottle of physiologic electrolyte solution not containing Pitocin.
c. Attach (piggyback) the Pitocin-containing bottle with the infusion pump to the infusion line as close to the infusion site as possible.
2. Administration
The initial dose should be 0.5–1 mU/min (equal to 3–6 mL of the dilute oxytocin solution per hour). At 30–60 minute intervals the dose should be gradually increased in increments of 1–2 mU/min until the desired contraction pattern has been established. Once the desired frequency of contractions has been reached and labor has progressed to 5–6 cm dilation, the dose may be reduced by similar increments.
Studies of the concentrations of oxytocin in the maternal plasma during Pitocin infusion have shown that infusion rates up to 6 mU/min give the same oxytocin levels that are
found in spontaneous labor. At term, higher infusion rates should be given with great care, and rates exceeding 9–10 mU/min are rarely required. Before term, when the sensitivity of the uterus is lower because of a lower concentration of oxytocin receptors, a
higher infusion rate may be required.
3. Monitoring
a. Electronically monitor the uterine activity and the fetal heart rate throughout the infusion of Pitocin. Attention should be given to tonus, amplitude and frequency of contractions, and to the fetal heart rate in relation to uterine contractions. If uterine contractions become too powerful, the infusion can be abruptly stopped, and oxytocic stimulation of the uterine musculature will soon wane (see PRECAUTIONS section).
b. Discontinue the infusion of Pitocin immediately in the event of uterine hyperactivity and/or fetal distress. Administer oxygen to the mother, who preferably should be put in a lateral position. The condition of mother and fetus should immediately be evaluated by the responsible physician and appropriate steps taken.
B. Control of Postpartum Uterine Bleeding
1. Intravenous infusion (drip method). If the patient has an intravenous infusion running, 10 to 40 units of oxytocin may be added to the bottle, depending on the amount of electrolyte or dextrose solution remaining (maximum 40 units to 1000 mL). Adjust the infusion rate to sustain uterine contraction and control uterine atony.
2. Intramuscular administration. (One mL) Ten (10) units of Pitocin can be given after the delivery of the placenta.
C. Treatment of Incomplete, Inevitable, or Elective Abortion
Intravenous infusion of 10 units of Pitocin added to 500 mL of a physiologic saline solution or 5% dextrose-in-water solution may help the uterus contract after a suction or
sharp curettage for an incomplete, inevitable, or elective abortion.
Subsequent to intra-amniotic injection of hypertonic saline, prostaglandins, urea, etc., for midtrimester elective abortion, the injection-to-abortion time may be shortened by infusion of Pitocin at the rate of 10 to 20 milliunits (20 to 40 drops) per minute. The total
dose should not exceed 30 units in a 12-hour period due to the risk of water intoxication.
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27075756
Using the BV-2 microglial cell line and primary mouse microglia, it was found that oxytocin (0.1, 1, and 10 μM) pre-treatment significantly inhibited LPS-induced microglial activation and reduced subsequent release of pro-inflammatory factors.
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ACTIVE MOIETY |
Structural Modifications
| Modification Type | Location Site | Location Type | Residue Modified | Extent | Fragment Name | Fragment Approval |
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| AMINO ACID SUBSTITUTION | [1_9] | GLYCINE | GLYCINAMIDE | 4JDT453NWO | ||
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Anhydrous citric acid | XF417D3PSL |
| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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| MOL_WEIGHT:SEQUENCE(CALCULATED) | CHEMICAL |
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| Molecular Formula | CHEMICAL |
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