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Oxytocin
Oxytocin Male Enhancement Supplements Mammalian Hormone Autism

Oxytocin Male Enhancement Supplements Mammalian Hormone Autism

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.

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description
Oxytocin
 

Oxytoxin Molecular structure

 Oxytocin Molecule

 

Sequence: CYIQNCPLG-NH2
Molecular formula: C43H66N12O12S2
Molar Mass: 1007.19 g/mol
CAS number: 158861-67-7
PubChem: CID 439302



Oxytocin
 


 

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 OXT gene.

 

Oxytocin is a peptide of nine amino acids (a nonapeptide). Its systematic name is cysteine-tyrosine-isoleucine-glutamine-asparagine-cysteine-proline-leucine-glycine-amine (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.[73] 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.

 

Romantic attachment:

 

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 reproductive tissue".

 

Maternal behavior:

 

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.

 

Sexual arousal:

 

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 arousal.

Studies using oxytocin antagonists in female rats provide data that oxytocin increases lordosis behavior, indicating an increase in sexual receptivity.

 


 

 

Oxytocin Description

 

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 formula is:

 

  

 

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

 

IMPORTANT NOTICE:

 

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.
 

 

Antepartum
 

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.

 

 

Postpartum

 

Oxytocin injection (synthetic) is indicated to produce uterine contractions during the third stage of labor and to control postpartum bleeding or hemorrhage.

 

Contraindications

 

Oxytocin injection (synthetic) is contraindicated in any of the following conditions:

  • Significant cephalopelvic disproportion;

  • Unfavorable fetal positions or presentations which are undeliverable without conversion prior to delivery, i.e., transverse lies;

  • 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.

 

Warnings

 

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.

 

 

Precautions

 

General

 

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 immediately available.

 

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 tetanic spasm.

 

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 mouth.

 

 

Drug Interactions

 

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 cyclopropane anesthesia.

 

 

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 as indicated.

 

Nursing Mothers

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.

Adverse Reactions

The following adverse reactions have been reported in the mother:

  • Anaphylactic reaction

  • Postpartum hemorrhage

  • Cardiac arrhythmia

  • Fatal afibrinogenemia

  • Nausea

  • Vomiting

  • Premature ventricular contractions

  • Pelvic hematoma

Excessive dosage or hypersensitivity to the drug may result in uterine hypertonicity, spasm, tetanic contraction or rupture of the uterus.

 

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 infant:

Due to induced uterine mobility:

  • Bradycardia

  • Premature ventricular contractions and other arrhythmias

  • Permanent CNS or brain damage

  • Fetal death

Due to use of Oxytocin in the mother:

  • Neonatal retinal hemorrhage

  • Low Apgar scores at five minutes

  • Neonatal jaundice

 

Overdosage

 

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 diluent.

 

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 of infusion.

 

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 placenta.

 

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 drops/minute.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

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