Vasopressin 1A receptor (V1AR). The prosocial effects of AVP are mediated by the V1AR, as they are blocked by the selective V1AR antagonist SR49059. [2]

In Chinese hamster ovary cells expressing rat or human V1b receptors, AVP (0.01 nM-1 μM) causes an elevation in Ca2+[2].

---

The binding affinity of endogenous vasopressin for its receptors can be significantly reduced or eliminated by single amino acid substitutions at key structural areas of the receptor. A natural example is seen in nephrogenic diabetes insipidus, where a point mutation affecting arginine disrupts the V2 receptor structure. [1]
Both vasopressin and oxytocin receptors show the capacity to form hetero-, homo-, or oligo-dimers in vitro, though the biological importance of this in vivo is unclear. [1]

Application of AVP to rat hippocampal tissue sections increased the frequency of inhibitory signals. This process occurs due to AVP binding to AVPR1a, which, through a G-protein mediated cascade, increases the excitability of interneurons, leading to increased GABA release. Concurrently, AVP has an excitatory effect on principal neurons (of pyramidal type) in this circuit. [1]

Vasopressin (0.03-0.3μg/kg; ip) enhances corticotropin secretion after body water loss and amplifies corticotropin release triggered by exogenous corticoliberin[2]. ? Potently increasing nearby laying, vasopressin (0.001-0.1μg/kg; ip) causes rats to lie passively next to one other when they first meet[3].

---

In adult male Long-Evans rats tested in a social interaction paradigm, peripheral intraperitoneal (IP) administration of AVP induces dose-dependent prosocial effects. A significant increase in "adjacent lying" (passive side-by-side contact) is observed at doses of 0.005 and 0.01 mg/kg, compared to saline and other doses tested (0.001 and 0.1 mg/kg). The maximal effect on adjacent lying is seen at 0.01 mg/kg. [2]
AVP at doses of 0.005, 0.01, and 0.1 mg/kg significantly reduces anogenital sniffing and rearing behavior compared to saline and the 0.001 mg/kg dose. The highest dose tested (0.1 mg/kg) reduces general investigation time compared to all other conditions. [2]
The prosocial effects of AVP (0.01 mg/kg), including increased adjacent lying and decreased anogenital sniffing, are completely prevented by pretreatment with the selective V1AR antagonist SR49059 (1 mg/kg, IP). [2]
When a sub-threshold dose of AVP (0.0025 mg/kg, which alone does not affect social behavior) is combined with a sub-threshold dose of MDMA (2.5 mg/kg), a robust and significant increase in adjacent lying is observed, along with a significant decrease in anogenital sniffing. This combination effect is greater than that of either drug alone. [2]

Adult male Long-Evans rats (250-300 g) were housed in groups under a reverse 12:12 h light-dark cycle and handled daily for 7 days before testing. All drugs were administered via intraperitoneal (IP) injection at a volume of 1 ml/kg. AVP was purchased from AusPep Ltd and dissolved in physiological saline (0.9%) to produce doses of 0.001, 0.0025, 0.005, 0.01, and 0.1 mg/kg. [2]
**Social Interaction Test:** Rats were tested in black rectangular arenas lined with bedding, under dim red light. On the day before testing, rats were individually habituated to the arena for 60 min. On test days, rats were weight-paired (±10 g) with an unfamiliar conspecific given the same drug treatment. Rats were placed in the test arena for 30 min, starting 10 min after AVP injection. Behaviors scored by a blind observer included adjacent lying, general investigation, anogenital sniffing, and rearing. A counterbalanced design was used for the dose-response study, with each rat receiving all doses of AVP and saline, with two washout days between treatments and a new partner each time. [2]
**Antagonist Study Protocol (Experiment 5):** In a between-groups design, pairs of rats (N=4 per condition) were administered either (1) vehicle + vehicle, (2) SR49059 (1 mg/kg) + vehicle, (3) vehicle + AVP (0.01 mg/kg), or (4) SR49059 (1 mg/kg) + AVP (0.01 mg/kg). Injections were given 15 min apart, and rats were tested for social interaction for 30 min, starting 10 min after the second injection. SR49059 was dissolved in a vehicle of 15% DMSO, 2% Tween-80, and 83% saline. [2]
**Drug Combination Protocol (Experiment 9):** In a between-groups design, pairs of rats (N=4 per condition) were randomly assigned to (1) saline + saline, (2) saline + AVP (0.0025 mg/kg), (3) saline + MDMA (2.5 mg/kg), or (4) AVP (0.0025 mg/kg) + MDMA (2.5 mg/kg). Injections were administered 10 min apart, and the 30-min test began 10 min after the second injection. [2]

---

Adult male Long-Evans rats (250-300 g) were housed in groups under a reverse 12:12 h light-dark cycle and handled daily for 7 days before testing. All drugs were administered via intraperitoneal (IP) injection at a volume of 1 ml/kg. AVP was purchased from AusPep Ltd and dissolved in physiological saline (0.9%) to produce doses of 0.001, 0.0025, 0.005, 0.01, and 0.1 mg/kg. [2]
Social Interaction Test: Rats were tested in black rectangular arenas lined with bedding, under dim red light. On the day before testing, rats were individually habituated to the arena for 60 min. On test days, rats were weight-paired (±10 g) with an unfamiliar conspecific given the same drug treatment. Rats were placed in the test arena for 30 min, starting 10 min after AVP injection. Behaviors scored by a blind observer included adjacent lying, general investigation, anogenital sniffing, and rearing. A counterbalanced design was used for the dose-response study, with each rat receiving all doses of AVP and saline, with two washout days between treatments and a new partner each time. [2]
Antagonist Study Protocol (Experiment 5): In a between-groups design, pairs of rats (N=4 per condition) were administered either (1) vehicle + vehicle, (2) SR49059 (1 mg/kg) + vehicle, (3) vehicle + AVP (0.01 mg/kg), or (4) SR49059 (1 mg/kg) + AVP (0.01 mg/kg). Injections were given 15 min apart, and rats were tested for social interaction for 30 min, starting 10 min after the second injection. SR49059 was dissolved in a vehicle of 15% DMSO, 2% Tween-80, and 83% saline. [2]
Drug Combination Protocol (Experiment 9): In a between-groups design, pairs of rats (N=4 per condition) were randomly assigned to (1) saline + saline, (2) saline + AVP (0.0025 mg/kg), (3) saline + MDMA (2.5 mg/kg), or (4) AVP (0.0025 mg/kg) + MDMA (2.5 mg/kg). Injections were administered 10 min apart, and the 30-min test began 10 min after the second injection. [2]

Vasopressin is synthesized in the hypothalamus and secreted from the posterior pituitary gland into the peripheral circulation. It is also released centrally within the brain from hypothalamic neurons. Peripherally administered peptides appear to cross the blood-brain barrier into the cerebral spinal fluid (CSF) in very small amounts (e.g., <1%). [1]

[1]. Oxytocin and vasopressin: linking pituitary neuropeptides and their receptors to social neurocircuits. Front Neurosci. 2015 Sep 24;9:335.

[2]. Acute prosocial effects of oxytocin and vasopressin when given alone or in combination with 3,4-methylenedioxymethamphetamine in rats: involvement of the V1A receptor. Neuropsychopharmacology. 2013 Oct;38(11):2249-59.

[3]. Characterization of (2S,4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxy-phenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2-pyrrolidine carboxamide (SSR149415), a selective and orally active vasopressin V1b receptor antagonist. J Pharmacol Exp Ther. 2002 Mar;300(3):1122-30.

Vasopressin is a neuropeptide known to modulate social behavior, aggression, and anxiety. This study demonstrates for the first time that acute peripheral (IP) administration of AVP can produce robust prosocial effects in rats, specifically increasing adjacent lying, which mimics the effects of MDMA and oxytocin. The study provides evidence that these prosocial effects are mediated by the V1A receptor, as they are blocked by the selective antagonist SR49059. The findings also suggest a commonality of action between AVP, oxytocin, and MDMA in stimulating social behavior, potentially via the V1AR. The synergistic effect of combining sub-threshold doses of AVP and MDMA further supports this common mechanism and may have implications for developing safer therapeutic approaches for social disorders or PTSD. [2]

1049.45

11000-17-2

11979316

White to off-white solid powder

1.509

27

32

38

148

4030

0

N1(C(C2NC(=O)C(CC(=O)N)NC(=O)C(CCC(=O)N)NC(=O)C(C(CC)C)NC(=O)C(CC3=CC=C(O)C=C3)NC(=O)C(N)CSSC2)=O)CCCC1C(NC(C(=O)N(C(=O)N)C)CCC/N=C(/N)\N)=O

KBZOIRJILGZLEJ-LGYYRGKSSA-N

InChI=1S/C46H65N15O12S2/c47-27-22-74-75-23-33(45(73)61-17-5-9-34(61)44(72)56-28(8-4-16-53-46(51)52)39(67)54-21-37(50)65)60-43(71)32(20-36(49)64)59-40(68)29(14-15-35(48)63)55-41(69)31(18-24-6-2-1-3-7-24)58-42(70)30(57-38(27)66)19-25-10-12-26(62)13-11-25/h1-3,6-7,10-13,27-34,62H,4-5,8-9,14-23,47H2,(H2,48,63)(H2,49,64)(H2,50,65)(H,54,67)(H,55,69)(H,56,72)(H,57,66)(H,58,70)(H,59,68)(H,60,71)(H4,51,52,53)/t27-,28-,29-,30-,31-,32-,33-,34-/m0/s1

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

argipressinH-Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2 (Disulfide Bridge Cys1-Cys6)arginine vasopressin (AVP) Vasopressin antidiuretic hormone (ADH)

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 : ~100 mg/mL (~92.23 mM)
H2O : ~50 mg/mL (~46.12 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.31 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.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (2.31 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.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (2.31 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.

---

Solubility in Formulation 4: 25 mg/mL (23.06 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with heating and sonication.

---

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