WAY-267464 is a non-peptide drug with a novel mechanism of action (MOA) to treat psychosis and schizophrenia.[1]
WAY-267464 is a non-peptide oxytocin receptor (OTR) agonist (EC50 = 61-881 nM; Ki = 58-978 nM) that, unlike oxytocin (OT), displays antagonist instead of agonist activity toward vasopressin V1a receptor/V1aR (IC50 = 613 nM; Ki = 27-113 nM). WAY-267464 exhibits OT-like anxiolytic effects in assays measuring both behavioral (33% increase in punished crossing by 10 mg/mL ip or 10 μg/mouse icv in four-plate tests; 75% increased open quadrants stay by 3 μg/mouse icv in elevated zero maze) and autonomic (47% higher stress-induced hyperthermia by 10 μg/mouse icv) parameters of the anxiety response. Similar to the antipsychotic-like effects reported for OT, WAY-267464 also reverses disruption in prepulse inhibition of the acoustic startle reflex induced by either MK-801 or amphetamine. Unlike OT, WAY-267464 does not affect immobility in mouse tail suspension test.
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11 - Combustible Solids
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WGK 3
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Oxytocin (OT) was reported to affect cognitive and emotional behavior by action in ventral tegmental area (VTA) and other brain areas. However, it is still unclear how OT activates VTA and related midline nucleus. Here, using patch-clamp recording, we studied
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
The oxytocinergic system promotes social behavior and reduces anxiety. The significant roles and functional interactions of the medial prefrontal cortex and the amygdala in the regulation of fear provide a unique experimental setting to examine the effects of oxytocin on
European journal of medicinal chemistry, 108, 730-740 (2016-01-08)
A previously identified, non-peptidic oxytocin (OT) receptor agonist WAY-267,464 (1) and nine novel derivatives (3, 4a-7a, 4b-7b) were synthesised and evaluated in vitro with the aim of systematically exploring hydrogen bonding interactions and ligand flexibility. All analogues were subjected to competition
British journal of pharmacology, 171(11), 2868-2887 (2014-03-20)
There is current interest in oxytocin (OT) as a possible therapeutic in psychiatric disorders. However, the usefulness of OT may be constrained by peripheral autonomic effects, which may involve an action at both OT and vasopressin V1A receptors. Here, we
