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Oxytocin and Vasopressin Agonists and Antagonists as Research Tools and Potential Therapeutics
Open accessAbstract
We recently reviewed the status of peptide and nonpeptide agonists and antagonists for the V 1a , V 1b and V 2 receptors for arginine vasopressin (AVP) and the oxytocin receptor for oxytocin (OT). In the present review, we update the status of peptides and nonpeptides as: (i) research tools and (ii) therapeutic agents. We also present our recent findings on the design of fluorescent ligands for V 1b receptor localisation and for OT receptor dimerisation. We note the exciting discoveries regarding two novel naturally occurring analogues of OT. Recent reports of a selective VP V 1a agonist and a selective OT agonist point to the continued therapeutic potential of peptides in this field. To date, only two nonpeptides, the V 2 /V 1a antagonist, conivaptan and the V 2 antagonist tolvaptan have received Food and Drug Administration approval for clinical use. The development of nonpeptide AVP V 1a , V 1b and V 2 antagonists and OT agonists and antagonists has recently been abandoned by Merck, Sanofi and Pfizer. A promising OT antagonist, Retosiban, developed at Glaxo SmithKline is currently in a Phase II clinical trial for the prevention of premature labour. A number of the nonpeptide ligands that were not successful in clinical trials are proving to be valuable as research tools. Peptide agonists and antagonists continue to be very widely used as research tools in this field. In this regard, we present receptor data on some of the most widely used peptide and nonpeptide ligands, as a guide for their use, especially with regard to receptor selectivity and species differences.
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“Although these compounds bind selectively to their respective receptors in rodents, they have now been shown to exhibit relatively high affinities for both OXTR and AVPR1a in primates (27,28).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [28]
In the citing paper
“Simply comparing the binding characteristics of the most common ligands for the human and rat OT and AVP receptors reveals considerable variation in pharmacological properties across species (28).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [28]
In the citing paper
“For example, studies employing recombinant expression systems to examine selectivity of human, rat, and mouse OT and AVP receptors have shown that only the human OTR is selective for OT using a standard criterion [34; 35] (Table 1).”
From Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery (2018) · cites this paper as [35]
In the citing paper
“The limited information on the distributions of OTR and V1aR in primate neural tissue is due in part to the lower selectivity for radioligands targeting OTR (125I-OVTA) and V1aR (125I-LVA) autoradiography, relative to high selectivity of radioligands for these receptors in rodents, as well as the promiscuous binding profile of both radioligands for OTR and V1aR (Freeman et al., 2014a, 2014b; Man”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Manning et al., 2012
In the citing paper
“There was also no difference in AVP levels, suggesting no peripheral cross-reactivity, which is more likely to occur with higher levels of oxytocin exposure.71”
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Self-citation
Flagged first, then by citations
Research works printed but not linked: 13
- Manning M, 1981, The Pituitary, 265
- Manning M, 1985, Development of Selective Agonists and Antagonists of Vasopressin and Oxytocin, 131
- Manning M, 1991, Vasopressin, 297
- Manning M, 2005, Peptides 2004, 101
- Lebl M, 1988, Handbook of Neurohypophyseal Hormone Analogs, 17
- Jard S, 1998, Adv Exp Med Biol, 1
- 10.1210/en.137.9.3906 · DOI
- Wisniewski K, 2010, Peptides 2010, 306
- Manning M, 2010, Peptides 2010, 366
- Guillon G, 2007, Peptides 2006, 742
- 10.1021/jm010526 · DOI
- Mimoun MB, 2001, Peptides 2000, 589
- Reichert J, 2010, Development Trends for Peptide Therapeutics
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“However, this study used [3H] OT and, like [3H] VP, [3H] OT may not exclusively bind OTR (Mouillac et al., 1995; Manning et al., 2012), and thus possibly may mask potential sex differences in OTR binding.”
MethodNeuromodulation by Oxytocin and Vasopressin
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Metadata
- Authors
- Manning, M., Misicka, A., Olma, A., Bankowski, K., Stoev, S., Chini, B., Durroux, T., Mouillac, B., Corbani, M., & Guillon, G.
- Affiliations
- University of Toledo (US)
- University of Warsaw (PL)
- Lodz University of Technology (PL)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Manning, M.
- Venue
- Journal of Neuroendocrinology
- Publisher
- Wiley
- Published
- 2012-03-26
- Volume
- 24
- Issue
- 4
- Pages
- 609-628
- ISSN
- 0953-8194 (ISSN-L)
- 1365-2826
- PMC
- PMC3490377
- OpenAlex
- W1803779312
- Cited by
- 423
- References
- 244
- Citations by year
- 2026: 14 · 2025: 20 · 2024: 22 · 2023: 25 · 2022: 32 · 2021: 36 · 2020: 31 · 2019: 40 · 2018: 34 · 2017: 35 · 2016: 28 · 2015: 29 · 2014: 38 · 2013: 30 · 2012: 8
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroendocrinology (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Centre National de la Recherche Scientifique
- National Institute of General Medical Sciences (GM25280, R01GM025280)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Keywords
- oxytocin, vasopressin, vasopressin receptor, oxytocin receptor, V1a receptor, V1b receptor, V2 receptor, peptide agonists, peptide antagonists, conivaptan, tolvaptan, fluorescent ligands, receptor localization, receptor dimerization, oxytocin analogues, receptor selectivity, species differences
- MeSH terms
- Animals, Arginine Vasopressin, Clinical Trials as Topic, Drug Evaluation, Preclinical, Humans, Oxytocin, Structure-Activity Relationship, Receptors, Vasopressin, Receptors, Oxytocin, Antidiuretic Hormone Receptor Antagonists
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