50-56-6 Usage
Uses
Used in Obstetrics and Gynecology:
Oxytocin is used as a peptide hormone for inducing labor and therapeutic abortions. It stimulates uterine contractions, which helps in the progression of labor, and is essential for the initiation and maintenance of milk ejection by the mammary glands.
Used in Neurotransmission:
Oxytocin acts as a neurotransmitter, playing a significant role in social memory and attachment, sexual and maternal behavior, and aggression. It is also implicated in various non-social behaviors, including learning, anxiety, feeding, and pain perception.
Used in the Regulation of Sodium Excretion:
Oxytocin is used to increase Na+ excretion, which helps in maintaining electrolyte balance and blood pressure regulation.
Used in the Stimulation of Myometrial GTPase and Phospholipase C:
Oxytocin stimulates myometrial GTPase and phospholipase C, which are essential for uterine contractions and the overall process of parturition.
In recent years, the safety of oxytocin has been greatly enhanced by the use of continuous maternal and fetal monitoring and controlled intravenous infusion of the drug, making it a more reliable and effective treatment option in various medical applications.
Receptors
One specific OT receptor (OTR) has been identified. In
humans, the OTR gene is located on chromosome 3 at
locus 3p25–26.2, and it encodes a protein of 389 aa residues. In most mammals, the OTR gene consists of three
exons while in the human and mouse, an additional
intron interrupts the first exon (consequently yielding
four exons). Estrogen stimulates OTR expression in the
uterus. Complete and/or half-palindromic EREs are
found in the promoters of OTR genes. Estrogen-induced
OTR expression in the brain is abolished in ER-alpha
knockout (KO) mice, whereas the basal OTR expression
of the KO mice is similar to that in controls. One OTR
has also been found in the holocephalan elephant fish. In elephant fish, a high expression of OTR is found in
the muscle and uterus.?OTR couples to Gq/11 and phospholipase C pathways. In addition, OTR activation leads to phosphorylation and
activation of the MAPK pathway in uterine myometrial
cells. OTR also activates the RhoA-Rho-kinase cascade,
which in turn leads to inhibition of myosin phosphatase.
The stimulation of nitric oxide production represents an
additional signaling pathway to mediate vasodilation,
natriuresis, and ANP release.
Indications and Usage
Oxytocin (OT) is a type of uterine contraction drug and can be derived from the animal posterior pituitary or chemically synthesized.
Oxytocin is a uterine contraction drug that is mostly used in late pregnancy induction and stagnant birth due to weak uterine contractions. Suitable for inducing labor and alleviating pain. Commonly used with ergot preparations to be used in inducing labor, expediting labor, and in uterine bleeding due to weak uterine contractions following birth or still birth. Nose drops can be used to promote lactation.
Mechanisms of Action
Oxytocin does not contain vasopressin and has no pressure-boosting effects. It can be absorbed through oral mucosa, selectively excite smooth uterine muscle, and intensify its contractions. The uterus is most sensitive to oxytocin when in labor (due to increased estrogen secretion), and an immature uterus will not respond to this drug. During early or mid-term pregnancy, the uterus has a relatively low reactivity to oxytocin, which gradually increases during late-stage pregnancy and peaks during labor. Small doses can strengthen the rhythmic contractions of smooth uterine muscles, increase their contractibility, increase their contraction speed, ensure similar contraction characteristics to that of a natural birth, and maintain polarity and symmetry. Thus, it is used clinically to expedite and induce labor. Large doses cause tonic contractions in the uterine muscles, so it is used clinically to burst blood vessels between muscle fibers, prevent postpartum hemorrhage, and ensuring postpartum recovery. It can also promote lactation by causing the breast ducts to contract and expel milk from the breasts, but it cannot increase the lactation amount.
Pharmacokinetics
Ineffective when taken orally, as it can be damaged by digestive fluids, although it can be absorbed through oral mucosa. 1-3 minutes of venous infusion 0.01 IU can induce physiological uterine contractions (Rhythmic, polar, symmetrical) with a short time span, as its half-life is only 2.5-3 minutes. Large doses cause tonic uterine contractions.
Adverse reactions
Oxytocin derived from cow or pig’s pituitary occasionally causes allergic reactions, and infusing too quickly may lead to mild vasodilation and hypotension. Patients who suffer from abruptio placentae, heart disease, or enlarged uterus, are over 35 years old, have a history of cesarean section or uterine muscle tumor removal, or are experiencing a breech birth should use with caution. Using oxytocin while experiencing a sacral block may lead to severe hypertension and even cerebrovascular rupturing. Cannot be injected in the same solution with norepinephrine. Incompatible with hydrolyzed proteins.
Contradictions
Do not use during birth if there are obvious signs of an unsymmetrical head, incorrect fetal position, exposed umbilical cord, prolapse, complete placenta previa, narrow pelvis, or overly intense uterine contractions. Not to be used by patients with overly narrow pelvises, histories of uterine surgery (including C-sections), excessive pains, blocked birth canals, abruptio placentae, or pregnancy poisoning.
Warnings and Precautions
Dosage and infusion speed must be strictly monitored when used to expedite or induce labor to prevent tonic contractions, which can suffocate the fetus or rupture the uterus.
Originator
Syntocinon,Sandoz,US,1957
Therapeutic Function
Oxytocic
Biosynthesis
Oxytocin is a cyclic nonapeptide that differs from vasopressin by only 2 amino acids. It is synthesized as a larger precursor molecule in cell bodies of the paraventricular nucleus, and to a lesser extent, the supraoptic nucleus in the hypothalamus. The precursor is rapidly converted by proteolysis to the active hormone and its neurophysin, packaged into secretory granules as an oxytocin-neurophysin complex, and secreted from nerve endings that terminate primarily in the posterior pituitary gland. In addition, oxytocinergic neurons that regulate the autonomic nervous system project to regions of the hypothalamus, brainstem, and spinal cord. Other sites of oxytocin synthesis include the luteal cells of the ovary, the endometrium, and the placenta.
Health Hazard
Uterine contraction, milk ejection, facilitates sperm ascent in female tract Decreases membrane potential of myometrium, basic metabolic rate, and liver glycogen Stimulates oviposition in hen, releases luteinizing hormone (LH) Increases blood sugar and urinary sodium and potassium
Biochem/physiol Actions
Oxytocin (OXT) and arginine vasopressin hormone plays a vital role in regulation of water excretion, parturition and lactation. OXT has been implicated in hydromineral homeostasis and vascular and cardiac relaxation. Oxytocin might function as an effective therapeutic for psychiatric diseases, including depression, schizophrenia, anxiety disorders, and autism. OXT has a potential as a marker of autism severity. OXT is an anorexigenic neuropeptide, which is implicated in social cognition and obsessive-compulsive behavior. Plasma oxytocin levels are high in children with Prader-willi syndrome (PWS) compared with unrelated and unaffected siblings. Deficiency of OXT hormone might contribute to pathogenesis of attention deficit/hyperactivity disorder (ADHD).
Clinical Use
Oxytocin is a potent uterine stimulant that is used for the induction and augmentation of labor, antenatal fetal assessment, and control of postpartum hemorrhage. If used improperly, oxytocin can lead to such complications as uterine hypercontractility with fetal distress, uterine rupture, maternal hypotension, water intoxication, and iatrogenic prematurity. These complications can almost always be avoided if oxytocin is given in proper dosages and with careful fetal and maternal monitoring.
Safety Profile
Poison by intravenous route. Experimental reproductive effects. A pituitary hormone which stimulates uterine contraction and milk production. The principal uterus-contracting and lactation-stimulating hormone of the posterior pituitary gland.Note: Unlike
Veterinary Drugs and Treatments
In veterinary medicine, oxytocin has been used for induction or
enhancement of uterine contractions at parturition, treatment of
postpartum retained placenta and metritis, uterine involution after
manual correction of prolapsed uterus in dogs, and in treating
agalactia.
Purification Methods
It is a cyclic nonapeptide which is purified by countercurrent distribution between solvent and buffer. It is soluble in H2O, n-BuOH and isoBuOH. [Bodanszky & du Vigneaud J Am Chem Soc 81 2504 1959, Cash et al. J Med Pharm Chem 5 413 1962, Sakakibara et al. Bull Chem Soc Jpn 38 120 1965; solid phase synthesis: Bayer & Hagenmyer Tetrahedron Lett 2037 1968.] It was also synthesised on a solid phase matrix and finally purified as follows: A Sephadex G-25 column is equilibrated with the aqueous phase of a mixture of 3.5% AcOH (containing 1.5% of pyridine)/n-BuOH/*C6H6 (2:1:1) and then the organic phase of this mixture is run through. A solution of oxytocin (100mg) in H2O (2mL) is applied to the column which is then eluted with the organic layer of the above mixture. The fractions containing the major peak [as determined by the Folin-Lowry protein assay: Fryer et al. Anal Biochem 153 262 1986] are pooled, diluted with twice their volume of H2O, evaporated to a small volume and lyophilised to give oxytocin as a pure white powder (20mg, 508 U/mg). [Ives Can J Chem 46 2318 1968, Beilstein 22 III/IV 82.]
Check Digit Verification of cas no
The CAS Registry Mumber 50-56-6 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 0 respectively; the second part has 2 digits, 5 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 50-56:
(4*5)+(3*0)+(2*5)+(1*6)=36
36 % 10 = 6
So 50-56-6 is a valid CAS Registry Number.
InChI:InChI=1S/C43H66N12O12S2/c1-5-22(4)35-42(66)49-26(12-13-32(45)57)38(62)51-29(17-33(46)58)39(63)53-30(20-69-68-19-25(44)36(60)50-28(40(64)54-35)16-23-8-10-24(56)11-9-23)43(67)55-14-6-7-31(55)41(65)52-27(15-21(2)3)37(61)48-18-34(47)59/h8-11,21-22,25-31,35,56H,5-7,12-20,44H2,1-4H3,(H2,45,57)(H2,46,58)(H2,47,59)(H,48,61)(H,49,66)(H,50,60)(H,51,62)(H,52,65)(H,53,63)(H,54,64)/t22-,25-,26-,27-,28-,29-,30-,31-,35-/m0/s1
50-56-6Relevant articles and documents
Improved Fmoc Solid-Phase Peptide Synthesis of Oxytocin with High Bioactivity
Sun, Pengcheng,Tang, Wenli,Huang, Yu,Hu, Bi-Huang
, p. 1780 - 1784 (2017)
We described here the synthesis of oxytocin by an improved Fmoc solid-phase peptide synthesis (SPPS) method with a Rink-Amide resin as the solid support, HBTU as the coupling reagent, Fmoc-protected amino acids as the building blocks, and piperazine for Fmoc removal as a substitute for the standard reagent piperidine. Unlike previously reported syntheses, the removal of the S -Acm protecting group of Cys and cyclization forming the disulfide bond were carried out by using iodine on the resin with the fully protected peptide chains. Finally, a crude oxytocin with a purity of 92% was obtained by simultaneous cleavage of the peptide chains from the resin and removal of all side-chain protecting groups with trifluoroacetic acid containing the scavengers (yield 85%). The crude peptide was purified by using preparative RP-HPLC to obtain oxytocin (high purity 99.3%) with a bioactivity of 588 IU/mg, the highest reported so far in the literature. This investigation provides a contribution in efforts for the large-scale synthesis of oxytocin in high purity under mild conditions with iodine for on-resin disulfide bond formation and a substitute for the standard Fmoc-deprotecting reagent piperidine, a controlled substance.
Disulfide bond formation in S-Acetamidomethyl cysteine-containing peptides by the combination of silver trifluoromethanesulfonate and dimethylsulfoxide / aqueous HCI
Tamamura, Hirokazu,Otaka, Akira,Nakamura, Junko,Okubo, Kaori,Koide, Takaki,Ikeda, Kyoko,Fujii, Nobutaka
, p. 4931 - 4934 (1993)
S-Acetamidomethyl (Acm) cysteine was found to be converted quantitatively to cystine by deprotection of the Acm group with silver trifluoromethanesulfonate (AgOTf) followed by dimethylsulfoxide (DMSO) / aqueous hydrochloric acid (HCl) treatment. No significant side reactions were observed with oxidation-sensitive amino acids such as Met, Tyr, and Trp under these reaction conditions. This method has been applied successfully to the syntheses of oxytocin and a Trp-containing peptide, urotensin II.
APPLICATION OF DIMETHYLSULFOXIDE(DMSO)/TRIFLUOROACETIC ACID(TFA) OXIDATION TO THE SYNTHESIS OF CYSTINE-CONTAINING PEPTIDE
Otaka, Akira,Koide, Takaki,Shide, Atsuko,Fujii, Nobutaka
, p. 1223 - 1226 (1991)
S-protected cysteine derivatives as well as cysteine were converted to cystine by action of DMSO/TFA; as examples, two model peptides, oxytocin and an α-human calcitonin gene-related peptide (α-hCGRP), were prepared by this reaction.
(S)-9-Fluorenylmethyl-L-cysteine, a Useful HF-stable Derivative for Peptide Synthesis
Ruiz-Gayo, Mariano,Albericio, Fernando,Pedroso, Enrique,Giralt, Ernest
, p. 1501 - 1502 (1986)
The reliability of the (S)-9-fluorenylmethyl-L-cysteine, a completely HF-stable cysteine derivative, has been tested on a solid phase synthesis of oxytocin.
“On-Resin” Disulfide Peptide Synthesis with Methyl 3-Nitro-2-pyridinesulfenate
Kobayashi, Kiyotaka,Taguchi, Akihiro,Cui, Yan,Shida, Hayate,Muguruma, Kyohei,Takayama, Kentaro,Taniguchi, Atsuhiko,Hayashi, Yoshio
supporting information, p. 956 - 963 (2021/02/01)
New methodologies for the construction of full peptide structures with all disulfide bonds on the resin are attractive for the development of solid phase peptide synthesis. Detailed reaction conditions for the on-resin disulfide bond formation have been investigated using a mild and chemically stable oxidizing reagent, methyl 3-nitro-2-pyridinesulfenate (Npys-OMe). Monocyclic oxytocin, MCH and bicyclic α-conotoxin ImI were synthesized in both semi-automated and full-automated protocols. It was found that on-resin intramolecular disulfide bond formation with Npys-OMe proceeds with the minimal formation of peptide oligomers by adopting a solvent system with 0.4 M LiCl/DMF. Crude peptides with complete disulfide bond patterns can be obtained in high purity using both protocols. This minimized the RP-HPLC purification step and the desired peptides were obtained with better yields. To our knowledge, this is the first fully automated construction of a bicyclic disulfide peptide on resin with more than 50 % purity in Fmoc-based SPPS. These results suggest that Npys-OMe is a useful reagent for the disulfide bond formation in automated protocols.
Detection of Thiol Functionality and Disulfide Bond Formation by Polyoxometalate
Konno, Hiroyuki,Yasumiishi, Haruto,Aoki, Reika,Nitanai, Ikumi,Yano, Shigekazu
supporting information, p. 745 - 749 (2020/11/10)
The detection of thiol functionality and intramolecular disulfide bond formation of peptides using the α-Keggin type polyoxometalate molybdenum-oxygen cluster (H3PMo12O40·nH2O) is described. Our method entails the addition of this polyoxometalate to solutions of thiol, whereupon the color of the solution changes from colorless to deep blue. Reduction of the polyoxometalate from Mo(VI) to Mo(V) occurs with concomitant oxidation of the thiol functionality, to form disulfide bonds. To exemplify the utility this phenomenon, we accomplished the oxidation of glutathione, reduced linear oxytocin, bactenecin, and α-conotoxin SI; all of which proceeded smoothly and in good conversion in 24 h to less and were accomplished by a change in the color of the reaction solutions.
Sustainable Peptide Synthesis Enabled by a Transient Protecting Group
Avrutina, Olga,Knauer, Sascha,Koch, Niklas,Kolmar, Harald,Meusinger, Reinhard,Uth, Christina
supporting information, p. 12984 - 12990 (2020/06/01)
The growing interest in synthetic peptides has prompted the development of viable methods for their sustainable production. Currently, large amounts of toxic solvents are required for peptide assembly from protected building blocks, and switching to water as a reaction medium remains a major hurdle in peptide chemistry. We report an aqueous solid-phase peptide synthesis strategy that is based on a water-compatible 2,7-disulfo-9-fluorenylmethoxycarbonyl (Smoc) protecting group. This approach enables peptide assembly under aqueous conditions, real-time monitoring of building block coupling, and efficient postsynthetic purification. The procedure for the synthesis of all natural and several non-natural Smoc-protected amino acids is described, as well as the assembly of 22 peptide sequences and the fundamental issues of SPPS, including the protecting group strategy, coupling and cleavage efficiency, stability under aqueous conditions, and crucial side reactions.
Selective disulfidation reagent using nitrogen-containing compound and method for producing disulfide-containing compound
-
Page/Page column 26-28; 34-35; 39, (2020/12/02)
The present invention provides a means capable of selectively introducing a disulfide bond with respect to two free thiol groups located in a molecule of an organic compound such as a peptide, or the like, in a short time by a simple treatment and also by a chemically stable method. A nitrogen-containing compound represented by Chemical Formula 1 below or a salt thereof: The symbols shown in Chemical Formula 1 are the same as defined in the specification.
Palladium-Mediated Direct Disulfide Bond Formation in Proteins Containing S-Acetamidomethyl-cysteine under Aqueous Conditions
Laps, Shay,Sun, Hao,Kamnesky, Guy,Brik, Ashraf
supporting information, p. 5729 - 5733 (2019/04/14)
One of the applied synthetic strategies for correct disulfide bond formation relies on the use of orthogonal Cys protecting groups. This approach requires purification before and after the deprotection steps, which prolongs the entire synthetic process and lowers the yield of the reaction. A major challenge in using this approach is to be able to apply one-pot synthesis under mild conditions and aqueous media. In this study, we report the development of an approach for rapid disulfide bond formation by employing palladium chemistry and S-acetamidomethyl-cysteine [Cys(Acm)]. Oxidation of Cys(Acm) to the corresponding disulfide bond is achieved within minutes in a one-pot operation by applying palladium and diethyldithiocarbamate. The utility of this reaction was demonstrated by the synthesis of the peptide oxytocin and the first total chemical synthesis of the protein thioredoxin-1. Our investigation revealed a critical role of the Acm protecting group in the disulfide bond formation, apparently due to the generation of a disulfiram in the reaction pathway, which significantly assists the oxidation step.
Rapid Photolysis-Mediated Folding of Disulfide-Rich Peptides
Patil, Nitin A.,Karas, John A.,Wade, John D.,Hossain, Mohammed Akhter,Tailhades, Julien
, p. 8599 - 8603 (2019/06/04)
Structure–activity relationship studies are a highly time-consuming aspect of peptide-based drug development, particularly in the assembly of disulfide-rich peptides, which often requires multiple synthetic steps and purifications. Therefore, it is vital to develop rapid and efficient chemical methods to readily access the desired peptides. We have developed a photolysis-mediated “one-pot” strategy for regioselective disulfide bond formation. The new pairing system utilises two ortho-nitroveratryl protected cysteines to generate two disulfide bridges in less than one hour in good yield. This strategy was applied to the synthesis of complex disulfide-rich peptides such as Rho-conotoxin ρ-TIA and native human insulin.
