Endogenous Metabolite
Oxytocin acetate targets oxytocin receptors and vasopressin V1a receptors. [1]
It acts on the oxytocin receptor (OXTR), and also binds to vasopressin receptors AVPR1A, AVPR1B, and AVPR2. It acts as an agonist on the transient receptor potential vanilloid-1 (TRPV1) receptor and as a positive allosteric modulator of the μ-opioid receptor (MOR). [2]

Oxytocin is a pleiotropic, peptide hormone with broad implications for general health, adaptation, development, reproduction, and social behavior. Endogenous oxytocin and stimulation of the oxytocin receptor support patterns of growth, resilience, and healing. Oxytocin can function as a stress-coping molecule, an anti-inflammatory, and an antioxidant, with protective effects especially in the face of adversity or trauma. Oxytocin influences the autonomic nervous system and the immune system. These properties of oxytocin may help explain the benefits of positive social experiences and have drawn attention to this molecule as a possible therapeutic in a host of disorders. However, as detailed here, the unique chemical properties of oxytocin, including active disulfide bonds, and its capacity to shift chemical forms and bind to other molecules make this molecule difficult to work with and to measure. The effects of oxytocin also are context-dependent, sexually dimorphic, and altered by experience. In part, this is because many of the actions of oxytocin rely on its capacity to interact with the more ancient peptide molecule, vasopressin, and the vasopressin receptors. In addition, oxytocin receptor(s) are epigenetically tuned by experience, especially in early life. Stimulation of G-protein-coupled receptors triggers subcellular cascades allowing these neuropeptides to have multiple functions. The adaptive properties of oxytocin make this ancient molecule of special importance to human evolution as well as modern medicine and health; these same characteristics also present challenges to the use of oxytocin-like molecules as drugs that are only now being recognized. SIGNIFICANCE STATEMENT: Oxytocin is an ancient molecule with a major role in mammalian behavior and health. Although oxytocin has the capacity to act as a "natural medicine" protecting against stress and illness, the unique characteristics of the oxytocin molecule and its receptors and its relationship to a related hormone, vasopressin, have created challenges for its use as a therapeutic drug [2].

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causing a decrease in core body temperature during the LMA task due to cognitive loss. Significantly more hypothermia was caused by subcutaneous injection of oxytocin acetate (0.1 mg/kg–0.3 mg/kg; single dose) than by oxytocin acetate (0.3 mg/kg) with saline or twice as much as 0.3 mg/kg oxytocin acetate 15–60 days after injection. While oxytocin acetate (0.1 mg/kg) created noticeably more batches at the 30-minute time point only, the temperature drop that was produced within minutes was much more than that of the excipient. [1] Oxytocin acetate (0.1 mg/kg) produced noticeably greater anogenital and body sniffing than saline. Additionally, it lengthens social engagement time overall (71.6 s)[1].

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In adult male Lister-hooded rats, Oxytocin acetate (0.03-0.3 mg/kg s.c.) dose-dependently affected locomotor activity and body temperature. The 0.3 mg/kg dose modestly reduced activity and caused significant hypothermia. The 0.1 mg/kg dose did not alter activity and had little effect on temperature. [1]
In adult male Lister-hooded rats, Oxytocin acetate (0.1 mg/kg s.c.) significantly attenuated phencyclidine (PCP)-induced hyperactivity, reducing locomotor activity by approximately 50% between 20 and 45 minutes after PCP injection. A lower dose (0.03 mg/kg) had no effect. [1]
In adult male Lister-hooded rats, Oxytocin acetate (0.1 mg/kg s.c.) significantly increased total social interaction time (71.6±4.3 s vs. 56.9±4.1 s in vehicle) between unfamiliar rats, particularly increasing body sniffing and anogenital sniffing. [1]
In the same rats, Oxytocin acetate (0.1 mg/kg s.c.) did not alter the number or pattern (flat, step, trill) of pro-social 50 kHz ultrasonic vocalizations (USVs). No 22 kHz USVs were emitted. [1]
In freely-moving rats, Oxytocin acetate (0.1 mg/kg s.c.) selectively elevated dopamine overflow in the nucleus accumbens (by ~100%) but not in the prefrontal cortex, and did not influence serotonin (5-HT) efflux in either brain region. [1]
In adult male Lister-hooded rats, Oxytocin acetate (0.1 mg/kg s.c.) caused a small (0.2-0.4°C) decrease in body temperature 30-45 minutes post-injection. [1]
The effects of Oxytocin acetate are dose-dependent, context-dependent, and sexually dimorphic. In individuals with a history of early life stress or trauma, exogenous oxytocin can have unpredictable or even negative consequences, such as increased symptoms in postpartum depression. [2]
In animal models, Oxytocin acetate treatment dampens the severity of stress- and chemical-induced colitis, reduces intestinal damage, oxidative stress, and anxiety-related behavior. It also protects the gut during reduced intestinal blood flow (e.g., in burn-induced gastric injury). [2]
In a mouse model of ischemic stroke, administration of exogenous Oxytocin acetate to animals recovering in social isolation recapitulated the neuroprotective effects of social housing, reducing tissue damage, increasing antioxidant activity, and decreasing oxidative stress. [2]
In an adult mouse model of acute brain inflammation induced by lipopolysaccharide (LPS), intranasal administration of Oxytocin acetate (1 hour prior to LPS) reduced microglial activation, levels of proinflammatory cytokines TNF-α and IL-1β, and levels of proinflammatory mediators COX-2 and iNOS in the prefrontal cortex. These anti-inflammatory actions were only observed in the presence of a stressor (LPS). [2]
In healthy men, intravenous infusion of Oxytocin acetate plus LPS attenuated the endocrine, cytokine, and chemokine response compared to men administered LPS alone. [2]
In male mice subjected to maternal separation stress, intracerebroventricular injection of Oxytocin acetate in adulthood attenuated the depressive-like phenotype and accompanying inflammation (impaired mitochondrial function, reduced antioxidant activity, increased oxidative stress, increased proinflammatory gene expression). This effect was blocked by the OXTR antagonist atosiban. [2]
In a rat model of diabetic polyneuropathy, Oxytocin acetate reduced visceral hypersensitivity. [2]
In a rodent model of necrotizing enterocolitis, Oxytocin acetate administration decreased the severity of intestinal inflammation. [2]
In a mouse model of autism, the oxytocin metabolite OT 4-9 (derived from the oxytocin molecule) produced a dose-dependent increase in prosocial behaviors without changing anxiety measures, an effect that persisted for 12 days after a subchronic regimen. [2]

Analysis of monoamines[1]
Microdialysis samples were analyzed using High Performance Liquid Chromatography with electrochemical detection as described previously. Defrosted samples were kept on ice before injection (15 µl) into a Targa C18 3 µM column (100 × 1.0 m) using a Perkin Elmer Series 200 autosampler. Dopamine, 5-HT and their major metabolites; 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were detected using a mobile phase (20 mM potassium dihydrogen phosphate, 20 mM sodium acetate, 0.1 mM ethylenediaminetetraacetic acid, 0.15 mM octanesulfonic acid, and 10% methanol, pH 3.9) at 0.4 ml/min (Dionex P680 pump), and measured against standards with a DECADE II SDC Detector I and Clarity software using a potential of + 0.75 V. The percentage change from baseline for every microdialysate molecule was calculated for each individual rat. PFC samples were excluded from one rat due to incorrect probe placement and two others because of flow disruption. In one rat NAc dopamine was below the detection limit; n = 6/7 per group in the PFC, and n = 7/8 in the NAc.

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Animal/Disease Models: 50 - six male Lister-hooded rats (150–200 g) [1]
Doses: 0.1 mg/kg-0.3 mg/kg
Route of Administration: subcutaneous injection; 0.1 mg/kg-0.3 mg/kg; Single dose
Experimental Results: produced Dramatically higher hypothermia (0.3 mg/kg) compared to the saline group.

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Dose–response and antagonist studies with oxytocin on core body temperature and locomotor activity[1]
To establish a suitable dose of oxytocin, which would not suppress locomotor activity (LMA) or produce hypothermia during microdialysis studies, rats (n = 12) were tested using a within-subjects design on four occasions at weekly intervals following injection of vehicle and each dose of oxytocin (0.03, 0.1, or 0.3 mg/kg s.c.) in a pseudo-random order to serve as their own control. This range was selected from previous reports showing that oxytocin doses above 0.3 mg/kg s.c. or i.p. suppress spontaneous locomotion in other rat strains so we included lower doses to identify those devoid of this unwanted effect. To establish the relative contribution of oxytocin and vasopressin V1a receptors to hypothermia produced by the highest dose, a further 12 rats received vehicle or oxytocin (0.3 mg/kg s.c.) in the presence and absence of the non-peptide selective V1a receptor antagonist SR49059 (1 mg/kg i.p.) or the selective oxytocin antagonist L-368,899 (2 mg/kg i.p.), on six occasions at weekly intervals (within-subjects design). Although original peptide antagonists for these receptors showed poor stability and selectivity the development of non-peptide antagonists greatly improved pharmacokinetic properties. The current non-peptide antagonists (SR49059 and L-368,889) were selected because they possess the best overall profile of commercially available oxytocin and V1a antagonists; having high affinity, relative selectivity, good BBB penetration, and plasma half-life and are devoid of partial agonist activity. Doses of these brain penetrant antagonists were selected from previous studies showing < 15 min onset and 2–4 h duration in rodents. SR49059 prevented oxytocin-induced pro-social behavior and hypothermia, whereas L-368,899 (which has brain penetration demonstrated by PET studies), prevented anxiolytic effects of oxytocin in the open field, reduced conditioned disgust behavior during social interaction and attenuated sexual motivation in male rats]. The cross-over repeat within-subject design for dose–response and antagonist studies greatly reduced the number of rats required and the inter-individual variation of measurements made in line with the 3 R’s principle.

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Doses and routes of administration:
Compounds were dissolved in 0.154 M saline (vehicle also containing 5% dimethyl sulfoxide for the antagonists) and administered at volume of 1 ml/kg subcutaneous (s.c.) (oxytocin)

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Effect of oxytocin on PCP-induced hyperactivity, social interaction, and PFC and NAc dopamine and 5-HT efflux[1]
Oxytocin at 0.03 and 0.1 mg/kg were selected for further investigation, as these doses did not produce confounding effects on ambulation and body temperature in dose–response studies described above. A separate group of rats (n = 32, Figure S1) was used to examine the effect of these two doses on PCP-induced hyperactivity, and on the basis of these findings 0.1 mg/kg oxytocin was administered 7 days later, prior to assessment of social interaction and USVs. The following week rats underwent stereotaxic surgery to implant microdialysis probes into the PFC and NAc and after 7 days recovery the effects of oxytocin on dopamine efflux from these brain regions was assessed. One week was left between each of the three protocols (Figure S1) to ensure complete drug wash-out and minimize any carry over effects from the previous procedure.

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Locomotor activity[1]
LMA was assessed on a single occasion as described above. Animals received oxytocin or vehicle after 30 min arena habituation, and vehicle or PCP (5.6 mg/kg i.p.; an established dose to examine “antipsychotic-like” activity) 30 min later, resulting in four treatment combinations: vehicle + vehicle, PCP + vehicle, PCP + 0.03 mg/kg oxytocin, PCP + 0.1 mg/kg (n = 8/group; between-subjects design).

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Locomotor Activity & Body Temperature Dose-Response: Male Lister-hooded rats (n=12) were tested in a within-subjects design. Oxytocin acetate (0.03, 0.1, or 0.3 mg/kg) or vehicle (0.154 M saline) was administered subcutaneously (s.c.) at a volume of 1 ml/kg after 30 min of arena habituation. Core body temperature was recorded via subcutaneously implanted microchips at 15 min intervals. Locomotor activity was recorded for 2 h using a dual-level photobeam activity system. [1]
Antagonist Study: Rats (n=12) received the V1a receptor antagonist SR49059 (1 mg/kg i.p.), the oxytocin receptor antagonist L-368,899 (2 mg/kg i.p.), or vehicle, 15 min prior to Oxytocin acetate (0.3 mg/kg s.c.) or vehicle, in a within-subjects design on six occasions. Body temperature and locomotor activity were measured as above. [1]
PCP-Induced Hyperactivity: Rats (n=8/group) received Oxytocin acetate (0.03 or 0.1 mg/kg s.c.) or vehicle after 30 min arena habituation, followed 30 min later by PCP (5.6 mg/kg i.p.) or vehicle. Locomotor activity was recorded for 90 min. Body temperature was also measured. [1]
Social Interaction: Two unfamiliar rats (weight-matched, from different litters, n=8 pairs/group) both received Oxytocin acetate (0.1 mg/kg s.c.) or vehicle 45 min before placement into a circular arena for 10 min under low light. Interactive behaviors were recorded and scored using Ethovision. Body temperature was recorded via telemetry before and after the trial. [1]
Microdialysis: One week after stereotaxic surgery to implant guide cannulae into the prefrontal cortex (PFC) and nucleus accumbens (NAc), microdialysis probes were inserted. The following day, three 20-minute baseline samples were collected before and for 2 h after injection of either Oxytocin acetate (0.1 mg/kg s.c.) or saline (1 ml/kg). [1]
Routes of Administration: Oxytocin acetate was administered subcutaneously (s.c.) in rats at a volume of 1 ml/kg. It has also been administered intraperitoneally (i.p.), intracerebroventricularly, intranasally, intravenously, and orally in various studies. [1, 2]
Oral Administration in Pre-weaning Mice: Oxytocin acetate has been shown to be resistant to digestion and active in milk and colostrum, with effects on brain and behavior when administered orally, especially in pre-weaning animals. Transport across the intestinal epithelium is mediated by the receptor for advanced glycation end products (RAGE). [2]
Nanoparticle Encapsulation: Recent methods to increase bioavailability involve nanoparticle encapsulation of Oxytocin acetate, which increases its prosocial effects and sustains behavioral changes for at least 3 days after intranasal treatment in mouse models. [2]

The blood-brain barrier (BBB) penetration of Oxytocin acetate is extremely low (as little as 0.01% of systemic dose may reach the rat CNS). The estimated blood half-life is ~5 min, but the cerebrospinal fluid half-life is considerably longer (at least 20 min). [1]
Endogenous oxytocin in human blood is typically at low concentrations of approximately 5 pg/ml, with small pulses (~15 pg/ml) sufficient for physiological effects. However, some methods (e.g., mass spectrometry) have indicated concentrations >500-1000 pg/ml, possibly due to oxytocin binding to other molecules like glutathione. [2]
Local tissue concentrations can be much higher; within ovarian tumors, oxytocin levels were measured at 200 times higher than in plasma. [2]
Oxytocin acetate is degraded by insulin-regulated aminopeptidase (IRAP), which cleaves the C-terminal tail to form MIF-1. It can also be degraded by other peptidases into a linear form. [2]
The disulfide bonds in Oxytocin acetate allow it to be highly reactive and form temporary unions with other thiol-containing molecules (e.g., glutathione) and phospholipids, affecting its measurement and bioavailability. [2]
The receptor for advanced glycation end products (RAGE) acts as an oxytocin-binding protein, facilitating the transport of oxytocin across the blood-brain barrier (5-10 times higher from blood to brain) and across the intestinal epithelium. [2]
Intranasally administered oxytocin labeled with deuterium has been detected in the cerebrospinal fluid and brain regions of monkeys. [2]

In rats, Oxytocin acetate at 0.3 mg/kg s.c. produced significant hypothermia (~2°C decrease), which was attenuated by the V1a receptor antagonist SR49059 but not by the oxytocin receptor antagonist L-368,899. The same dose caused a modest but significant reduction in cumulative locomotor activity. [1]
High doses of Oxytocin acetate (1 or 2 mg/kg i.p.) have been shown to suppress spontaneous locomotion in other rat strains (Wistar, Sprague-Dawley). [1]
High doses of exogenous oxytocin can cause receptor desensitization and internalization (e.g., in the uterus), leading to decreased responsiveness. [2]
In the context of birth, higher doses of exogenous oxytocin (Pitocin) may confer less neuroprotection in vitro and are associated with an increased risk for autism in male offspring, possibly due to receptor desensitization, fetal oxygen desaturation from uterine hyperstimulation, or promiscuous binding to proinflammatory AVPR1A. [2]
The relationship between oxytocin and cancer is complex. While oxytocin can inhibit tumor growth in some cancers (e.g., breast cancer), it can increase proliferation in others (e.g., prostate, uterine, small cell lung cancer), depending on the local availability of oxytocin/receptor, tumor cell type, and differential activation of subcellular signaling pathways (Gαq vs. Gαi/Gαs). [2]
In women with postpartum depression and a history of early life stress, intranasal Oxytocin acetate increased depressive symptoms, whereas it decreased symptoms in those without such a history. [2]

[1]. Oxytocin attenuates phencyclidine hyperactivity and increases social interaction and nucleus accumben dopamine release in rats. Neuropsychopharmacology. 2019 Jan;44(2):295-305.

[2]. Is Oxytocin "Nature's Medicine"? Pharmacol Rev. 2020 Oct;72(4):829-861.

See also: Oxytocin (containing active ingredient)... See more...

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Oxytocin acetate is a nine-amino acid peptide hormone (Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2) with a disulfide bond between the two cysteine residues. It was the first peptide hormone to be biochemically described and synthesized. [1, 2]
Precursors or extended forms of oxytocin (OT-X, consisting of 10, 11, or 12 amino acids) are biologically active and are found in mammalian fetuses. A failure to modify the oxytocin precursor may produce a less-active form, potentially elevated in autistic individuals. [2]
Fragments of oxytocin are biologically active. For example, the C-terminal fragment MIF-1 (OT 7-9, Pro-Leu-Gly-NH2) regulates pain via opioid receptor interactions, acts as an antidepressant, and is a positive allosteric modulator of D2/D4 dopamine receptors. The linear form of oxytocin acts to stimulate α-2 adrenoreceptors. [2]
The effects of Oxytocin acetate are mediated by G-protein-coupled receptors (GPCRs) and activate various subcellular cascades. OXTR can couple to different Gα subunits (Gαi, Gαs, Gαq), leading to separable functions (e.g., Gαq for muscle contraction and proliferation, Gαi/Gαs for antiproliferative effects). [2]
The oxytocin-vasopressin system is an integrated system, and oxytocin can readily bind to vasopressin receptors (especially AVPR1A), complicating its therapeutic use. [2]
The expression of the oxytocin receptor (OXTR) is epigenetically tuned by early life experience, including parental care and exogenous oxytocin exposure. For example, perinatal exposure to oxytocin (to model labor induction) in voles caused lasting changes in OXTR methylation patterns, social behavior, and receptor densities in the brain. [2]

C43H66N12O12S2.C2H4O2

1067.2393

1066.457

C, 50.64; H, 6.61; N, 15.75; O, 20.99; S, 6.01

6233-83-6

6233-83-6 (acetate);50-56-6;

12004215

Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2 (Disulfide bridge:Cys1-Cys6)

CYIQNCPLG-NH2 (Disulfide bridge:Cys1-Cys6)

White to off-white solid powder

Endogenous Metabolite

13

17

17

73

1900

9

CC(O)=O.O=C([C@H](CSSC[C@@H](C(N[C@H](C1=O)CC2=CC=C(O)C=C2)=O)N)NC([C@@H](NC([C@@H](NC(C(N1)[C@@H](C)CC)=O)CCC(N)=O)=O)CC(N)=O)=O)N(CCC3)[C@@H]3C(N[C@@H](CC(C)C)C(NCC(N)=O)=O)=O

DSZOEVVLZMNAEH-BXUJZNQYSA-N

InChI=1S/C43H66N12O12S2.C2H4O2/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;1-2(3)4/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);1H3,(H,3,4)/t22-,25-,26-,27-,28-,29-,30-,31-,35-;/m0./s1

(S)-N-((S)-1-((2-amino-2-oxoethyl)amino)-4-methyl-1-oxopentan-2-yl)-1-((4R,7S,10S,13S,16S,19R)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-13-((S)-sec-butyl)-16-(4-hydroxybenzyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacycloicosane-4-carbonyl)pyrrolidine-2-carboxamide acetate

Orasthin; Oxystin; Ossitocina; Pitocin; Oxoject; Piton S; Ossitocina; Oxetakain; Oxitocina; Partocon; Oxt; Oxytocin.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~125 mg/mL (~117.12 mM)
H2O : ~50 mg/mL (~46.85 mM)

Solubility in Formulation 1: 25 mg/mL (23.42 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)