Oxytocin

Oxytocin is a nine-residue peptide hormone, CYIQNCPLG-NH2, whose first and sixth cysteines are joined by a disulfide bond to form a six-residue ring with a three-residue amidated tail. This listing is a sealed vial of 2 mg of freeze-dried oxytocin, supplied as the acetate salt. Research on it spans the 1953 synthesis, the oxytocin receptor and its signalling, the chemistry of its breakdown in solution, and the quality of oxytocin sold as a medicine.

Handling notes

Unlike most peptides in this catalog, oxytocin carries a hazard classification of its own. The safety data sheet lists it as toxic if swallowed (H301) and toxic if inhaled (H331), able to cause allergy or asthma symptoms or breathing difficulties if inhaled (H334), able to cause an allergic skin reaction (H317), and as a category 1A reproductive toxicant that may damage fertility or the unborn child (H360). It also carries H413 for long-lasting harmful effects to aquatic life, and the SDS says to store it locked up.

Those statements apply to the powder in this vial. The precautionary statements and protective equipment are on the safety data sheet linked in the specifications. Keep the sealed vial frozen, desiccated and dark, at the temperature given in section 9 of the SDS, and let it reach room temperature before opening so moisture does not condense on the powder.

What the research covers

Structure and synthesis

Oxytocin is a cyclic nonapeptide with one internal disulfide bond, between the cysteines at positions 1 and 6¹. In the sequence Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2, glutamine sits at position 4, asparagine at 5 and an amidated glycine at 9, the three sites where deamidation has been found in acidic solution². The first synthesis was reported in 1953 by du Vigneaud's group, who described their product as an octapeptide amide with the hormonal activity of oxytocin³; the older convention counted the two bridged cysteines as a single cystine residue.

Where it is made and how the receptor signals

Gimpl and Fahrenholz's 2001 review describes oxytocin as made mainly in magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei and released from the posterior pituitary into the circulation in response to stimuli such as suckling, parturition and certain kinds of stress⁴. Oxytocinergic neurons also project widely within the central nervous system, and the peptide is synthesised in peripheral tissues including the uterus, placenta, corpus luteum, testis and heart⁴. The oxytocin receptor is a class I G protein-coupled receptor coupled mainly through Gq to phospholipase C-beta. Its high-affinity state requires both magnesium and cholesterol, and its agonist-binding region differs from the site where antagonists bind⁴. The review also stresses that the system's regulation depends strongly on steroids⁴.

The oxytocin receptor has close relatives in the vasopressin V1a, V1b and V2 receptors, and Manning and colleagues reviewed the peptide and non-peptide agonists and antagonists used to separate them in research⁵. Peptide ligands remained in very wide use as research tools, and several non-peptide compounds that failed in clinical trials were proving useful in the laboratory⁵.

Breakdown in solution

Hawe and colleagues followed oxytocin degradation at pH 2.0, 4.5, 7.0 and 9.0 and at temperatures from 40 to 80 °C². Loss of intact peptide was fastest at pH 9.0, then 7.0, then 2.0, and slowest at pH 4.5². At pH 2.0 the products were deamidated forms; at pH 4.5 and above they included tri- and tetrasulfides and dimers linked through disulfide or dityrosine bonds, with beta-elimination and larger aggregates also observed². Those experiments concerned solutions, and dry powder was not part of them.

Quality of medicinal oxytocin

Oxytocin is a widely used obstetric medicine, and its quality has been studied directly⁶. A 2016 systematic review pooled eight studies covering 559 samples from 15 low- and middle-income countries and found a median of 45.6% of samples failing quality tests, mostly because they held too little active ingredient⁶. Over a third of the samples had less than 90% of the stated content, and two contained none⁶. Those were finished medicines in their own supply chains, not research material.

What is not established

Most of what is known about oxytocin signalling in the brain comes from animal and cell work, and the oxytocin and neuronal circuits guide summarises those rodent circuit studies. The human behavioural literature, almost all of it from intranasal studies, is discussed on the oxytocin nasal spray page. None of the cited studies used SCALE Performance material.

Frequently asked questions

References

1. Wiśniewski K, Finnman J, Flipo M, et al. On the mechanism of degradation of oxytocin and its analogues in aqueous solution. Biopolymers. 2013;100(4):408-21. DOI · PubMed
2. Hawe A, Poole R, Romeijn S, et al. Towards heat-stable oxytocin formulations: analysis of degradation kinetics and identification of degradation products. Pharm Res. 2009;26(7):1679-88. DOI · PubMed
3. Vigneaud VD, Ressler C, Swan CJM, et al. THE SYNTHESIS OF AN OCTAPEPTIDE AMIDE WITH THE HORMONAL ACTIVITY OF OXYTOCIN. Journal of the American Chemical Society. 1953;75(19):4879-4880. DOI
4. Gimpl G, Fahrenholz F. The oxytocin receptor system: structure, function, and regulation. Physiol Rev. 2001;81(2):629-83. DOI · PubMed
5. Manning M, Misicka A, Olma A, et al. Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics. J Neuroendocrinol. 2012;24(4):609-28. DOI · PubMed
6. Torloni MR, Gomes Freitas C, Kartoglu UH, et al. Quality of oxytocin available in low- and middle-income countries: a systematic review of the literature. BJOG. 2016;123(13):2076-2086. DOI · PubMed