Oxytocin receptor ligands: a survey of the patent literature

Is oxytocin the hormone of happiness? Probably not. However, this small nine amino acid peptide is involved in a wide variety of physiological and pathological functions such as sexual activity, penile erection, ejaculation, pregnancy, uterus contraction, milk ejection, maternal behavior, osteoporosis, diabetes, cancer, social bonding, and stress, which makes oxytocin and its receptor potential candidates as targets for drug therapy. In this review, we address the issues of drug design and specificity and focus our discussion on recent findings on oxytocin and its heterotrimeric G protein-coupled receptor OTR. In this regard, we will highlight the following topics: (i) the role of oxytocin in behavior and affectivity, (ii) the relationship between oxytocin and stress with emphasis on the hypothalamo–pituitary–adrenal axis, (iii) the involvement of oxytocin in pain regulation and nociception, (iv) the specific action mechanisms of oxytocin on intracellular Ca2+ in the hypothalamo neurohypophysial system (HNS) cell bodies, (v) newly generated transgenic rats tagged by a visible fluorescent protein to study the physiology of vasopressin and oxytocin, and (vi) the action of the neurohypophysial hormone outside the central nervous system, including the myometrium, heart and peripheral nervous system. As a short nine amino acid peptide, closely related to its partner peptide vasopressin, oxytocin appears to be ideal for the design of agonists and antagonists of its receptor. In addition, not only the hormone itself and its binding to OTR, but also its synthesis, storage and release can be endogenously and exogenously regulated to counteract pathophysiological states. Understanding the fundamental physiopharmacology of the effects of oxytocin is an important and necessary approach for developing a potential pharmacotherapy.

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“…The following excellent reviews should be consulted for more complete descriptions, see Refs. [112,50,104].…”

Section: Towards An Oxytocin Receptor Therapymentioning

confidence: 99%

REVIEW: Oxytocin: Crossing the Bridge between Basic Science and Pharmacotherapy

Viero

Shibuya

Naoki

et al. 2010

CNS Neuroscience & Therapeutics

229

183

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“…As central Oxt is involved in many behaviors, the use of agonists and antagonists for peripheral indications will need close scrutiny to assess unintended behavioral effects due to passage of the agents through the blood brain barrier. Excellent reviews are available (Gimpl, 2008; Manning et al , 2008). …”

Section: Introductionmentioning

confidence: 99%

Oxytocin: The Great Facilitator of Life

Lee

Macbeth

Pagani

et al. 2009

Progress in Neurobiology

610

634

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Oxytocin (Oxt) is a nonapeptide hormone best known for its role in lactation and parturition. Since 1906 when its uterine-contracting properties were described until 50 years later when its sequence was elucidated, research focused on its peripheral roles in reproduction. Only over the past several decades have researchers focused on what functions Oxt might have in the brain, the subject of this review. Immunohistochemical studies revealed that magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei are the neurons of origin for the Oxt released from the posterior pituitary. Smaller cells in various parts of the brain, as well as release from magnocellular dendrites, provide the Oxt responsible for modulating various behaviors at its only identified receptor. Although Oxt is implicated in a variety of “non-social” behaviors, such as learning, anxiety, feeding and pain perception, it is Oxt’s roles in various social behaviors that have come to the fore recently. Oxt is important for social memory and attachment, sexual and maternal behavior, and aggression. Recent work implicates Oxt in human bonding and trust as well. Human disorders characterized by aberrant social interactions, such as autism and schizophrenia, may also involve Oxt expression. Many, if not most, of Oxt’s functions, from social interactions (affiliation, aggression) and sexual behavior to eventual parturition, lactation and maternal behavior, may be viewed as specifically facilitating

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“…OTR ligands with high specificity over the related AVP receptors are currently available and several patents propose their therapeutic utility in numerous applications, e.g. increasing lactation, acting against preterm labor, breast cancer, modulating immune system, osteoporosis, and autism-related disorders (reviewed in [ 15 ]). Potential novel application of OT include treatment of autism, schizophrenia, depression, social anxiety, and Prader-Willi syndrome [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Oxytocin and cardioprotection in diabetes and obesity

2016

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Oxytocin (OT) emerges as a drug for the treatment of diabetes and obesity. The entire OT system is synthesized in the rat and human heart. The direct myocardial infusion with OT into an ischemic or failing heart has the potential to elicit a variety of cardioprotective effects. OT treatment attenuates cardiomyocyte (CMs) death induced by ischemia-reperfusion by activating pro-survival pathways within injured CMs in vivo and in isolated cells. OT treatment reduces cardiac apoptosis, fibrosis, and hypertrophy. The OT/OT receptor (OTR) system is downregulated in the db/db mouse model of type 2 diabetes which develops genetic diabetic cardiomyopathy (DC) similar to human disease. We have shown that chronic OT treatment prevents the development of DC in the db/db mouse. In addition, OT stimulates glucose uptake in both cardiac stem cells and CMs, and increases cell resistance to diabetic conditions. OT may help replace lost CMs by stimulating the in situ differentiation of cardiac stem cells into functional mature CMs. Lastly, adult stem cells amenable for transplantation such as MSCs could be preconditioned with OT ex vivo and implanted into the injured heart to aid in tissue regeneration through direct differentiation, secretion of protective and cardiomyogenic factors and/or their fusion with injured CMs.

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Oxytocin receptor ligands: a survey of the patent literature

Cited by 12 publications

References 85 publications

REVIEW: Oxytocin: Crossing the Bridge between Basic Science and Pharmacotherapy

REVIEW: Oxytocin: Crossing the Bridge between Basic Science and Pharmacotherapy

Oxytocin: The Great Facilitator of Life

Oxytocin and cardioprotection in diabetes and obesity

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