Oxytoxin Molecular structure
Molecular formula: C43H66N12O12S2
Molar Mass: 1007.19 g/mol
CAS number: 158861-67-7
PubChem: CID 439302
Oxytocin is a mammalian hormone that acts primarily as a
neuromodulator in the brain. Oxytocin is best known for its roles
in sexual reproduction, in particular during and after childbirth.
It is released in large amounts after distension of the cervix and
uterus during labor, facilitating birth, and after stimulation of
the nipples, facilitating breastfeeding. The word oxytocin was
derived from the Greek word“, meaning quick birth. The oxytocin
peptide is synthesized as an inactive precursor protein from the
Oxytocin is a peptide of nine amino acids (a nonapeptide). Its
systematic name is
(cys, tyr, ile,gln,asn,cys, pro, leu, gly - NH2, or CYIQNCPLG-NH2).
The cysteine residues form a disulfide bond. Oxytocin has a
molecular mass of 1007 daltons.
One international unit (IU) of oxytocin is the equivalent of about
2 micrograms of pure peptide. The trust-inducing property of
oxytocin might help those who suffer from social anxieties and mood
disorders, but with the potential for abuse with confidence tricks
and military applications.
The structure of oxytocin is very similar to that of vasopressin
(cys,tyr,phe, gln,asn,cys, pro,arg,gly - NH2), also a nonapeptide
with a sulfur bridge, whose sequence differs from oxytocin by two
amino acids. A table showing the sequences of members of the
vasopressin/oxytocin super family and the species expressing them
is present in the vasopressin article. Oxytocin and vasopressin
were isolated and synthesized by Vincent du Vigneaud in 1953, work
for which he received the Nobel Prize in Chemistry in 1955.
Oxytocin and vasopressin are the only known hormones released by
the human posterior pituitary gland to act at a distance. However,
oxytocin neurons make other peptides, including
corticotropin-releasing hormone and dynorphin, for example, that
act locally. Oxytocin has peripheral (hormonal) actions, and also
has actions in the brain. Its actions are mediated by specific,
high-affinity oxytocin receptors. The oxytocin receptor is a
G-protein-coupled receptor that requires Mg2+ and cholesterol.
Does Oxytocin Play a Role in Autism?
Oxytocin may play a role in autism and may be an effective
treatment for autism's repetitive and affiliative behaviors.
Oxytocin treatments also resulted in an increased retention of
affective speech in adults with autism. Two related studies in
adults, in 2003 and 2007, found oxytocin decreased repetitive
behaviors and improved interpretation of emotions. More recently,
intranasal administration of oxytocin was found to increase emotion
recognition in children as young as 12 who are diagnosed with
autism spectrum disorders.
Oxytocin and the Gastro Tract
Oxytocin is destroyed in the gastrointestinal tract, so must be
administered by injection or as nasal spray. It has a half-life of
typically about three minutes in the blood, and given intravenously
does not enter the brain in significant quantities - it is excluded
from the brain by the blood-brain barrier. Evidence in rhesus
macaques indicates oxytocin by nasal spray does enter the brain.
Oxytocin nasal sprays have been used to stimulate breastfeeding,
but the efficacy of this approach is doubtful.
Neural Sources of Oxytocin
In the hypothalamus, oxytocin is made in magnocellular
neurosecretory cells of the supraoptic and paraventricular nuclei,
and is stored in Herring bodies at the axon terminals in the
posterior pituitary. Oxytocin is also made by some neurons in the
paraventricular nucleus that project to other parts of the brain
and to the spinal cord. Depending on the species, oxytocin
receptor-expressing cells are located in other areas, including the
amygdala and bed nucleus of the stria terminalis.
In the pituitary gland, oxytocin is packaged in large, dense-core
vesicles, where it is bound to neurophysin I. Secretion of oxytocin
from the neurosecretory nerve endings is regulated by the
electrical activity of the oxytocin cells in the hypothalamus.
Non-neural sources of Oxytocin
Outside the brain, oxytocin-containing cells have been identified
in several diverse tissues, including the corpus luteum, the
interstitial cells of Leydig, the retina, the adrenal medulla, the
placenta, the thymus and the pancreas. The finding of significant
amounts of this classically "neurohypophysial" hormone outside the
central nervous system raises many questions regarding its possible
importance in these different tissues.
The Leydig cells in some species have also been shown to possess
the biosynthetic machinery to manufacture testicular oxytocin de
novo, to be specific, in rats (which can synthesize vitamin C
endogenously), and in guinea pigs, which, like humans, require an
exogenous source of vitamin C (ascorbate).
Recent Research Related to Oxytocin and Effects
Research has shown that Oxytocin evokes feelings of contentment,
reductions in anxiety, and feelings of calmness and security around
the mate. Many studies have already shown a correlation of Oxytocin
with human bonding, increases in trust, and decreases in fear. One
study confirmed a positive correlation between Oxytocin plasma
levels and an anxiety scale measuring the adult romantic
attachment. This suggests Oxytocin may be important for the
inhibition of the brain regions associated with behavioral control,
fear, and anxiety, thus allowing orgasm to occur.
In some studies, high levels of plasma oxytocin have been
correlated with romantic attachment. For example, if a couple is
separated for a long period of time, anxiety can increase due to
the lack of physical affection. Oxytocin may aid romantically
attached couples by decreasing their feelings of anxiety when they
are separated. A study reported increases of oxytocin during sexual
arousal could be in response to nipple/areola, genital, and/or
genital tract stimulation as confirmed in other mammals.
Murphy et al. (1987), studying men, found oxytocin levels were
raised throughout sexual arousal with no acute increase at orgasm.
A more recent study of men found an increase in plasma oxytocin
immediately after orgasm, but only in a portion of their sample
that did not reach statistical significance. The authors noted
these changes "may simply reflect contractile properties on
Female rats given oxytocin antagonists after giving birth do not
exhibit typical maternal behavior. By contrast, virgin female sheep
show maternal behavior toward foreign lambs upon cerebrospinal
fluid infusion of oxytocin, which they would not do otherwise.
Oxytocin is involved in the initiation of maternal behavior, not
its maintenance; for example, it is higher in mothers after they
interact with unfamiliar children rather than their own.
Oxytocin injected into the cerebrospinal fluid causes spontaneous
erections in rats, reflecting actions in the hypothalamus and
spinal cord. Centrally administrated oxytocin receptor antagonists
can prevent noncontact erections, which is a measure of sexual
Studies using oxytocin antagonists in female rats provide data that
oxytocin increases lordosis behavior, indicating an increase in
Each mL of Oxytocin Injection, USP (synthetic), intended for
intravenous infusion or intramuscular injection, possesses an
oxytocic activity equivalent to 10 USP Oxytocin Units and contains
chlorobutanol anhydrous (chloral derivative) 0.5%. This product may
contain up to 12.5% decomposition products/impurities. Oxytocin
injection (synthetic) is a sterile, clear, colorless solution of
Oxytocin in Water for Injection prepared by synthesis. Acetic acid
may have been added for pH adjustment (pH 3.0-5.0). The structural
Oxytocin - Clinical Pharmacology
Oxytocin injection (synthetic) acts on the smooth muscle of the
uterus to stimulate contractions; response depends on the uterine
threshold of excitability. It exerts a selective action on the
smooth musculature of the uterus, particularly toward the end of
pregnancy, during labor and immediately following delivery.
Oxytocin stimulates rhythmic contractions of the uterus, increases
the frequency of existing contractions and raises the tone of the
uterine musculature. Synthetic Oxytocin does not possess the
cardiovascular effects, such as elevation of blood pressure, as
exhibited by vasopressin found in posterior pituitary injection.
Indications and Usage for Oxytocin
Oxytocin Injection, USP (synthetic) is indicated for the medical
rather than the elective induction of labor. Available data and
information are inadequate to define the benefits to risks
considerations in the use of the drug product for elective
induction. Elective induction of labor is defined as the initiation
of labor for convenience in an individual with a term pregnancy who
is free of medical indications.
Oxytocin injection (synthetic) is indicated for the initiation or
improvement of uterine contractions, where this is desirable and
considered suitable, in order to achieve early vaginal delivery for
fetal or maternal reasons. 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, pre-eclampsia at or
near term, when delivery is in the best interest 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) 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.
Oxytocin injection (synthetic) is indicated to produce uterine
contractions during the third stage of labor and to control
postpartum bleeding or hemorrhage.
Oxytocin injection (synthetic) is contraindicated in any of the
Significant cephalopelvic disproportion;
Unfavorable fetal positions or presentations which are
undeliverable without conversion prior to delivery, i.e.,
In obstetrical emergencies where the benefit-to-risk ratio for
either the fetus or the mother favors surgical intervention;
In cases of fetal distress where delivery is not imminent;
Prolonged use in uterine inertia or severe toxemia;
Hypertonic uterine patterns;
Patients with hypersensitivity to the drug;
Induction or augmentation of labor in those cases where vaginal
delivery is contraindicated, such as cord presentation or prolapse,
total placenta previa, and vasa previa.
Oxytocin injection (synthetic) when given for induction or
stimulation of labor, must be administered only by the intravenous
route and with adequate medical supervision in a hospital.
All patients receiving intravenous Oxytocin must be under
continuous observation by trained personnel with a thorough
knowledge of the drug and qualified to identify complications. A
physician qualified to manage any complications should be
When properly administered, Oxytocin should stimulate uterine
contractions similar to those seen in normal labor. Overstimulation
of the uterus by improper administration can be hazardous to both
mother and fetus. Even with proper administration and adequate
supervision, hypertonic contractions can occur in patients whose
uteri are hypersensitive to Oxytocin.
Except in unusual circumstances, Oxytocin should not be
administered in the following conditions: prematurity, borderline
cephalopelvic disproportion, previous major surgery on the cervix
or uterus including caesarean section, overdistention of the
uterus, grand multiparity or invasive cervical carcinoma. Because
of the variability of the combinations of factors which may be
present in the conditions above, the definition of ‘‘unusual
circumstances’’ must be left to the judgement of the physician. The
decision can only be made by carefully weighing the potential
benefits which Oxytocin can provide in a given case against rare
but definite potential for the drug to produce hypertonicity or
Maternal deaths due to hypertensive episodes, subarachnoid
hemorrhage, rupture of the uterus and fetal deaths due to various
causes have been reported associated with the use of parenteral
oxytocic drugs for induction of labor and for augmentation in the
first and second stages of labor.
Oxytocin has been shown to have an intrinsic antidiuretic effect,
acting to increase water reabsorption from the glomerular filtrate.
Consideration should, therefore, be given to the possibility of
water intoxication, particularly when Oxytocin is administered
continuously by infusion and the patient is receiving fluids by
Severe hypertension has been reported when Oxytocin was given three
to four hours following prophylactic administration of a
vasoconstrictor in conjunction with caudal block anesthesia.
Cyclopropane anesthesia may modify Oxytocin’s cardiovascular
effects, so as to produce unexpected results such as hypotension.
Maternal sinus bradycardia with abnormal atrioventricular rhythms
has also been noted when Oxytocin was used concomitantly with
Carcinogenesis, Mutagenesis, Impairment of Fertility
There are no animal or human studies on the carcinogenicity and
mutagenicity of this drug, nor is there any information on its
effect on fertility.
Pregnancy Category C.
There are no known indications for use of Oxytocin in the first and
second trimester of pregnancy other than in relation to spontaneous
or induced abortion. Based on the wide experience with this drug
and its chemical structure and pharmacological properties, it would
not be expected to present a risk of fetal abnormalities when used
It is not known whether this drug is excreted in human milk.
Because many drugs are excreted in human milk, caution should be
exercised when Oxytocin is administered to a nursing woman.
The following adverse reactions have been reported in the mother:
Excessive dosage or hypersensitivity to the drug may result in
uterine hypertonicity, spasm, tetanic contraction or rupture of the
The possibility of increased blood loss and afibrinogenemia should
be kept in mind when administering the drug.
Severe water intoxication with convulsions and coma has occurred,
and is associated with a slow Oxytocin infusion over a 24-hour
period. Maternal death due to Oxytocin-induced water intoxication
has been reported.
The following adverse reactions have been reported in the fetus or
Due to induced uterine mobility:
Due to use of Oxytocin in the mother:
Overdosage with Oxytocin injection (synthetic) depends essentially
on uterine hyperactivity whether or not due to hypersensitivity to
this agent. Hyperstimulation with strong (hypertonic) or prolonged
(tetanic) contractions, or a resting tone of 15 to 20 mm H2O or
more between contractions can lead to tumultuous labor, uterine
rupture, cervical and vaginal lacerations, postpartum hemorrhage,
uteroplacental hypoperfusion and variable deceleration of fetal
heart, fetal hypoxia, hypercapnia or death. Water intoxication with
convulsions, which is caused by the inherent antidiuretic effect of
Oxytocin, is a serious complication that may occur if large doses
(40 to 50 milliunits/minute) are infused for long periods.
Management consists of immediate discontinuation of Oxytocin, and
symptomatic and supportive therapy.
Oxytocin Dosage and Administration
Dosage of Oxytocin is determined by uterine response. The following
dosage information is based upon the various regimens and
indications in general use.
Induction or Stimulation of Labor
Intravenous infusion (drip method) is the only acceptable method of
administration for the induction or stimulation of labor.
Accurate control of the rate of infusion flow is essential. An
infusion pump or other such device and frequent monitoring of
strength of contractions and fetal heart rate are necessary for the
safe administration of Oxytocin for the induction or stimulation of
labor. If uterine contractions become too powerful, the infusion
can be abruptly stopped, and oxytocic stimulation of the uterine
musculature will soon wane.
An intravenous infusion of a non-Oxytocin containing solution
should be started. Physiologic electrolyte solutions should be used
except under unusual circumstances.
To prepare the usual solution for intravenous infusion–one mL (10
units) is combined aseptically with 1,000 mL of a non-hydrating
The combined solution, rotated in the infusion bottle to insure
thorough mixing, contains 10 mU/mL. Add the container with dilute
oxytocic solution to the system through the use of a constant
infusion pump or other such device to control accurately the rate
The initial dose should be no more than 1 to 2 mU/min. The dose may
be gradually increased in increments of no more than 1 to 2
mU/min., until a contraction pattern has been established which is
similar to normal labor.
The fetal heart rate, resting uterine tone, and the frequency,
duration, and force of contractions should be monitored.
The Oxytocin infusion should be discontinued immediately in the
event of uterine hyperactivity or fetal distress. Oxygen should be
administered to the mother. The mother and fetus must be evaluated
by the responsible physician.
Control of Postpartum Uterine Bleeding
Intravenous Infusion (Drip Method)—To control postpartum bleeding, 10 to 40 units of Oxytocin may be
added to 1,000 mL of a nonhydrating diluent and run at a rate
necessary to control uterine atony.
Intramuscular Administration—1 mL (10 units) of Oxytocin can be given after delivery of the
Treatment of Incomplete or Inevitable Abortion
Intravenous infusion with physiologic saline solution, 500 mL, or
5% dextrose in physiologic saline solution to which 10 units of
Oxytocin have been added should be infused at a rate of 20 to 40
Parenteral drug products should be inspected visually for
particulate matter and discoloration prior to administration,
whenever solution and container permit.