Oxytocin Receptor, also known as OXTR, OTR, is the receptor protein for oxytocin and is encoded by the OTR gene located on human chromosome 3p25. OTR protein belongs to the G protein-coupled receptor family. It is present in myoepithelial cells of the mammary gland, the myometrium at the end of pregnancy, and the endometrial cells. And it plays an important role in the induction of uterine contraction and lactation during labor. At the same time, OTR also relates to the central nervous system, affecting social, cognitive and emotional behavior. For example, down-regulation of the gene’s expression can lead to prenatal stress, postnatal depression, and social anxiety. Besides, OTR closely relates to the amygdala and fear-related responses. Studies have shown that OTR methylation down-regulation leads to increased grey matter in the amygdala and reduced parasympathetic tone.
Oxytocin (OT) is a peptide hormone that is synthesized in the hypothalamus and secreted by the posterior pituitary gland and can be released into the bloodstream. It responds to human sexual activity and has analgesic properties to facilitate labor clinically. Oxytocin also has applications for a variety of psychiatric disorders, including autism spectrum disorder, schizophrenia, depression and so on. However, endogenous OT has a short half-life in plasma and poor permeability across the blood-brain barrier.
WAY-267464 is a non-peptide oxytocin receptor agonist.
WAY-267464 is a first-generation non-peptide OTR agonist with a high affinity for OTR and effective blood-brain barrier permeability. According to the report, it is 100-fold more selective for OTR than V1AR, V1BR, and V2R. In addition to being an agonist of OTR, WAY-267464 also acts as an antagonist of the antidiuretic hormone 1A receptor and modulates social recognition memory. Moreover, WAY-267464 (i.p., 10 and 30 mg/kg) has antagonist effects on the Vasopressin (AVP)-induced (0.005 mg/kg) facilitation of social recognition at a retention interval of 120 min in rats. Also, WAY-267464 completely prevents the increase in preference for the novel over the familiar juvenile stimulus rat induced by AVP at 10 and 30 mg/kg but not 1 mg/kg.
In conclusion, WAY-267464 is a selective non-peptide oxytocin receptor (OTR) agonist, possessing a high affinity and blood-brain barrier permeability.