Neuropharmacology. 2010 Jan;58(1):69-77. Epub 2009 Jul 15.
Receptor and behavioral pharmacology of WAY-267464, a non-peptide oxytocin receptor agonist.

Ring RH, Schechter LE, Leonard SK, Dwyer JM, Platt BJ, Graf R, Grauer S, Pulicicchio C, Resnick L, Rahman Z, Sukoff Rizzo SJ, Luo B, Beyer CE, Logue SF, Marquis KL, Hughes ZA, Rosenzweig-Lipson S.

Discovery Neuroscience, Wyeth Research, CN8000, Princeton, NJ 08543, USA. ringr@wyeth.com

The widely reported effects of oxytocin (OT) on CNS function has generated considerable interest in the therapeutic potential for targeting this system for a variety of human psychiatric diseases, including anxiety disorders, autism, schizophrenia, and depression. The utility of synthetic OT, as both a research tool and neurotherapeutic, is limited by the physiochemical properties inherent in most neuropeptides, notably its short half-life and poor blood brain barrier penetration. Subsequently, the discovery and development of non-peptide molecules that act as selective agonists of the oxytocin receptor (OTR) has been an important goal of the field. In this study, we report the receptor and behavioral pharmacology of WAY-267464, a first generation small-molecule OTR agonist. WAY-267464 is a high-affinity, potent, and selective (vs. V1a, V2, V1b) agonist of the OTR. In assays measuring both behavioral (four-plate test, elevated zero maze) and autonomic (stress-induced hyperthermia) parameters of the anxiety response, WAY-267464 exhibits an anxiolytic-like profile similar to OT. We have demonstrated that the anxiolytic-like profile of WAY-267464 is mediated through central sites of action. WAY-267464 also significantly reverses disruption in prepulse inhibition of the acoustic startle reflex induced by either MK-801 or amphetamine, similar to the antipsychotic-like effects previously reported for OT. Interestingly, in the mouse tail suspension test, WAY-267464 failed to produce changes in immobility that are seen with OT, raising the question of whether the antidepressant-like activity of OT may be working independently of the OTR. A selective OTR antagonist also failed to block the effects of OT on immobility in the TST. The significance of these findings for shaping the clinical development of OTR agonists is discussed.

PMID: 19615387 [PubMed - in process]

Yes I am aware of paronia as a symptom of schizophrenia. However, I do not think of oxytocin as a purely trust hormone…I think of it as more of a social hormone…and it may enhance desire to indulge in social interactions and social inference- be it benign or malignant. I do stand by my assertion that peoplke with schizophrenia mentalize a lot , more so than others and paronia is just one way this manifest itself. It is unlikely you will get paranoid if you don’t think other have too much agency/mind or think about others a lot of the time. Thus, oxytocin may be more related to our ability to menatlize and thus to empathize or became paranoid based on that ability and different inclinations.

This post was mentioned on Twitter by Sandeep Gautam: check my new mouse trap post on epigenetics of autism : the oxytocin connection http://bit.ly/3grMDn...