Cerebral and extracerebral distribution of radioactivity associated with oxytocin in rabbits after intranasal administration: Comparison of TTA-121, a newly developed oxytocin formulation, with Syntocinon

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with deficits in social interactions/communication. Despite the large number of ASD patients, there is no drug approved to treat its core symptoms. Recently, Syntocinon (oxytocin nasal spray) has been reported to have a therapeutic effect on ASD. However, the disadvantage of Syntocinon for ASD treatment is that 6 puffs/administration are required to achieve the effective pharmacological dose. Furthermore, there are no published reports evaluating the cerebral distribution profile of oxytocin after intranasal administration. TTA-121 is a newly developed intranasal oxytocin formulation with high bioavailability produced by optimizing the physicochemical properties. In this study, we prepared the same formula as Syntocinon as the control formulation (CF), and the cerebral and extracerebral distribution of oxytocin in rabbits after single intranasal administration of (3)H-labeled oxytocin formulations—[(3)H]TTA-121 and [(3)H]CF were examined and compared. The area under the concentration-time curve to the time of the last quantifiable concentration (AUC(t)) in the whole brain was 3.6-fold higher in the [(3)H]TTA-121 group than in the [(3)H]CF group, indicating increased delivery of radioactivity to the brain by TTA-121 than by CF. Since the distribution profiles showed no notable differences in radioactivity between the olfactory bulb and trigeminal nerve, intranasally-administered oxytocin was probably transferred to the brain via both pathways. The results also showed an increase in radioactivity in the prefrontal area and the precuneus, which are probable sites of pharmacological action as shown in clinical studies using functional magnetic resonance imaging (fMRI), confirming that intranasally-administered oxytocin could reach these tissues.