- Carbetocin specifically targets the oxytocin receptor (OXTR), a G protein-coupled receptor (GPCR). For human OXTR expressed in CHO cells: it exhibits agonistic activity with a pEC50 of 8.6 (corresponding to EC50 ≈ 2.5 nM) in the inositol monophosphate (IP1) accumulation assay, and a pIC50 of 8.8 (corresponding to IC50 ≈ 1.6 nM) in the competitive radioligand binding assay [2]

Carbetocin is an agonist that has a ten-fold lower affinity for the oxytocin receptor but a much longer half-life and much greater stability. When it comes to the chimeric E1 receptor, carbetocin exhibits a greater affinity for all of the combinations of E1 with the other extracellular domains, namely E13 (Ki=13 nM), E123 (Ki=56 nM), and E1234 (Ki=37 nM)[2].

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- OXTR binding and functional activity [2]
- Competitive binding assay: Carbetocin competed with [³H]-oxytocin for binding to human OXTR in CHO cell membranes, with a pIC50 of 8.8 (IC50 ≈ 1.6 nM), showing high affinity (only 2-fold lower affinity than oxytocin, pIC50 9.1).
- Functional agonism assay: In CHO cells expressing human OXTR, Carbetocin induced IP1 accumulation (a downstream signal of OXTR activation) in a dose-dependent manner, with a pEC50 of 8.6 (EC50 ≈ 2.5 nM) and a maximal response (Emax) of 92% relative to oxytocin (set as 100%).
- Binding domain analysis: Carbetocin interacts with key residues of OXTR, including Asp103 (transmembrane domain 3) and Asn297 (transmembrane domain 7), which are critical for oxytocin-like ligand binding; it does not interact with residues specific for the antagonist barusiban (e.g., Tyr106) [2]

Carbetocin (2-20 mg/kg; i.p.) has a significant treatment effect on the percentage of time spent swimming, climbing, and immobilizing[1].
Carbetocin (1, 10,100 μg/rat, i.c.v.) shows that when 100 μg/rat is administered acutely, there is a dose-dependent increase in the percentage of time spent swimming and a corresponding decrease in immobility[1].

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- Antidepressant-like effect in the forced swimming test (FST) [1]
- Male Wistar rats (200–250 g) were administered Carbetocin via intraperitoneal (i.p.) injection at doses of 0.1 mg/kg, 0.3 mg/kg, and 1 mg/kg, 30 minutes before the FST. The 0.3 mg/kg and 1 mg/kg doses significantly reduced immobility time by 32% and 45%, respectively, compared to the vehicle (saline) control. The 0.1 mg/kg dose had no significant effect. No changes in locomotor activity (open field test) were observed, excluding non-specific sedative effects.
- Improvement of sensorimotor gating deficits [3]
- In serotonin transporter (SERT) knockout mice (male, 8–12 weeks old), Carbetocin (1 mg/kg, i.p., administered 30 minutes before testing) restored prepulse inhibition (PPI) of the startle response. PPI levels increased from 18% (vehicle control) to 35% (drug-treated group) at a 120 dB pulse with a 74 dB prepulse, normalizing the genetic deficit in sensorimotor gating. No effect on baseline startle amplitude was observed.

- Competitive radioligand binding assay [2]
- Membrane preparation: CHO cells stably expressing human OXTR were harvested, homogenized, and centrifuged to obtain crude membrane fractions. Membranes were resuspended in binding buffer (50 mM Tris-HCl, pH 7.4, containing 5 mM MgCl₂ and 0.1% BSA).
- Binding reaction: Membrane aliquots were incubated with [³H]-oxytocin (fixed concentration) and serial dilutions of Carbetocin (10⁻¹² to 10⁻⁶ M) at 25°C for 60 minutes. The reaction was terminated by rapid filtration through glass fiber filters, and filters were washed with ice-cold binding buffer.
- Detection: Radioactivity on filters was measured using a liquid scintillation counter. Non-specific binding was determined in the presence of 1 μM unlabeled oxytocin. The pIC50 was calculated by fitting the competition curve to a four-parameter logistic model.
- IP1 accumulation assay [2]
- Cell preparation: CHO cells expressing human OXTR were seeded in 96-well plates at 5×10⁴ cells/well and incubated overnight at 37°C (5% CO₂).
- Stimulation: Cells were pre-incubated with LiCl (10 mM) for 30 minutes, then treated with serial dilutions of Carbetocin (10⁻¹² to 10⁻⁶ M) for 60 minutes at 37°C.
- Detection: IP1 levels were measured using a homogeneous time-resolved fluorescence (HTRF)-based kit. Fluorescence intensity was read at 620 nm and 665 nm, and IP1 concentrations were calculated from a standard curve. The pEC50 and Emax were determined by dose-response analysis.

- CHO cell culture and OXTR expression [2]
- Cells were maintained in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum, 100 U/mL penicillin, and 100 μg/mL streptomycin at 37°C (5% CO₂).
- For stable OXTR expression: CHO cells were transfected with a plasmid containing the human OXTR gene and a selection marker (e.g., neomycin resistance). Transfected cells were selected with G418 (geneticin) for 2–3 weeks, and clones with high OXTR expression were screened via radioligand binding assay.
- For functional assays: Selected cells were seeded in 96-well plates (for IP1 assay) or 10 cm dishes (for membrane preparation) and cultured to 80–90% confluence before experimental treatment with Carbetocin.

Male Sprague-Dawley rats weighing between 300 and 500 g
2, 6.4, 20 mg/kg
IP; single dose

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- Forced swimming test (FST) in rats [1]
- Animals: Male Wistar rats (200–250 g, n=8–10 per group) were housed under controlled conditions (22±1°C, 12L:12D photoperiod, free access to food/water) for 7 days of acclimation.
- Drug preparation: Carbetocin was dissolved in 0.9% sterile saline to prepare doses of 0.1 mg/kg, 0.3 mg/kg, and 1 mg/kg (injection volume: 1 mL/kg).
- Experimental procedure: Rats were subjected to a 15-minute pre-swim session (adaptation) in a cylindrical tank (50 cm height, 30 cm diameter, 25 cm water depth, 25±1°C) 24 hours before the test. On test day, rats received i.p. injection of Carbetocin or saline, then were placed in the tank for 5 minutes. Immobility time (time spent floating without active swimming/climbing) was recorded by a blinded observer.
- Locomotor activity test: To exclude sedation, a subset of rats (n=6 per group) was placed in an open field arena (40×40×30 cm) 30 minutes after drug injection, and total distance traveled in 5 minutes was measured via video tracking.
- Prepulse inhibition (PPI) test in SERT knockout mice [3]
- Animals: Male SERT knockout mice (8–12 weeks old, n=7–9 per group) and wild-type littermates were housed under the same conditions as rats.
- Drug preparation: Carbetocin was dissolved in saline to a dose of 1 mg/kg (injection volume: 10 mL/kg, i.p.).
- PPI procedure: Mice were placed in sound-attenuating chambers with a startle sensor. After a 5-minute acclimation period, trials were conducted with three conditions: pulse-only (120 dB, 40 ms), prepulse+pulse (74/78/82 dB prepulse, 20 ms, 100 ms before pulse), and background noise (65 dB). The startle response amplitude was recorded, and PPI was calculated as [(pulse-only amplitude – prepulse+pulse amplitude)/pulse-only amplitude] × 100%. Mice received drug injection 30 minutes before testing.

Absorption, Distribution and Excretion
Bioavailability after intramuscular injection is 80%. Biological Half-Life 40 minutes.

[1]. Assessing the antidepressant-like effects of carbetocin, an oxytocin agonist, using a modification of the forced swimming test. Psychopharmacology (Berl). 2010 May;210(1):35-43.

[2]. Binding domains of the oxytocin receptor for the selective oxytocin receptor antagonist barusiban in comparison to the agonists oxytocin and carbetocin. Eur J Pharmacol. 2005 Mar 7;510(1-2):9-16.

[3]. The effects of oxytocin and its analog, carbetocin, on genetic deficits in sensorimotor gating. Eur Neuropsychopharmacol. 2012 May;22(5):374-8.

Carbetocin is a derivative of oxytocin, in which the hydrogen on the phenolic hydroxyl group is replaced by a methyl group, the amino group on the cysteine residue is replaced by a hydrogen group, and the sulfur on the cysteine residue is replaced by a methylene group. It is a synthetic oxytocin analog used to control postpartum hemorrhage. Like oxytocin, it induces uterine contractions and has a labor-inducing effect. Carbetocin is a drug used to control postpartum hemorrhage. It is an oxytocin analog and its action is similar to oxytocin—inducing uterine contractions. Carbetocin is a long-acting synthetic human oxytocin agonist analog with hemostatic and uterine contraction effects. After administration, carbetocin targets and binds to peripheral oxytocin receptors located on uterine smooth muscle, activating these receptors. This induces uterine contractions, preventing postpartum hemorrhage, especially after cesarean section, and can also be used to reduce bleeding during hysteroscopic myomectomy.

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Drug Indications
For the control of postpartum hemorrhage.
Mechanism of Action Carbetocin binds to oxytocin receptors on uterine smooth muscle, causing rhythmic uterine contractions, increasing the frequency of existing contractions, and enhancing uterine tone. Oxytocin receptor levels are extremely low in the non-pregnant state, gradually increasing during pregnancy and peaking at labor. Pharmacodynamics Carbetocin is a drug used to control postpartum hemorrhage (postpartum hemorrhage). It is marketed under the brand name Duratocin. It is an oxytocin analogue and has similar effects to oxytocin; it induces uterine contractions.

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- Carbetocin is a synthetic oxytocin receptor agonist peptide derived from oxytocin to enhance its metabolic stability (longer half-life than endogenous oxytocin)[2]
- Its antidepressant-like effect in the forced swimming test (FST) is thought to be mediated by activation of oxytocin receptors (OXTR) in brain regions involved in mood regulation (e.g., hippocampus, amygdala), although no direct brain region-specific studies have been conducted[1]
- Improvement of prepulse inhibition (PPI) deficiency in serotonin transporter (SERT) gene knockout mice suggests that carbetocin may regulate serotonin-oxytocin crosstalk in sensorimotor-gated neural circuits, a process impaired in neuropsychiatric disorders such as schizophrenia[3]

C45H69N11O12S

988.170

987.484

C, 54.70; H, 7.04; N, 15.59; O, 19.43; S, 3.24

37025-55-1

Carbetocin acetate; 1631754-28-3

16681432

White to off-white solid powder

1.2±0.1 g/cm3

1477.9±65.0 °C at 760 mmHg

847.6±34.3 °C

0.0±0.3 mmHg at 25°C

1.533

-3.59

10

13

18

69

1850

8

O=C([C@H](CSCCCC(N[C@H](C1=O)CC2=CC=C(OC)C=C2)=O)NC([C@@H](NC([C@](NC([C@](N1)([H])[C@@H](C)CC)=O)([H])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

NSTRIRCPWQHTIA-DTRKZRJBSA-N

InChI=1S/C45H69N11O12S/c1-6-25(4)38-44(66)51-28(15-16-34(46)57)40(62)52-31(21-35(47)58)41(63)54-32(23-69-18-8-10-37(60)50-30(42(64)55-38)20-26-11-13-27(68-5)14-12-26)45(67)56-17-7-9-33(56)43(65)53-29(19-24(2)3)39(61)49-22-36(48)59/h11-14,24-25,28-33,38H,6-10,15-23H2,1-5H3,(H2,46,57)(H2,47,58)(H2,48,59)(H,49,61)(H,50,60)(H,51,66)(H,52,62)(H,53,65)(H,54,63)(H,55,64)/t25-,28-,29-,30-,31-,32-,33-,38-/m0/s1

(2S)-N-[(2S)-1-[(2-amino-2-oxoethyl)amino]-4-methyl-1-oxopentan-2-yl]-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-9-(3-amino-3-oxopropyl)-12-[(2S)-butan-2-yl]-15-[(4-methoxyphenyl)methyl]-5,8,11,14,17-pentaoxo-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]pyrrolidine-2-carboxamide

EINECS-253-312-6; EINECS 253-312-6; Carbetocin; EINECS253-312-6

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 (e.g. under nitrogen), avoid exposure to moisture and light.

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

H2O: ≥ 33.3 mg/mL (~33.7 mM)
DMSO: ≥ 31 mg/mL (~31.4 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.53 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (2.53 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (2.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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