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.

Ishii D, Kageyama M, Umeda S

PloS one20 Dec 2021Cited by 7 (Europe PMC)

PMID34929003PMCIDPMC8687547DOI10.1371/journal.pone.0261451PepBankPUB-34929003

Summary

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 3H-labeled oxytocin formulations-[3H]TTA-121 and [3H]CF were examined and compared. The area under the concentration-time curve to the time of the last quantifiable concentration (AUCt) in the whole brain was 3.6-fold higher in the [3H]TTA-121 group than in the [3H]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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

3 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Pharmacokinetics
In rabbits given intranasal 3H-oxytocin, whole-brain AUCt of radioactivity was higher with the TTA-121 formulation than with the control formulation.
In plain wordsIn rabbits, the new oxytocin nasal formulation TTA-121 delivered more radioactivity to the brain than the standard formulation.
Peptide
Oxytocin
Outcome
IncreaseWhole-brain AUCt of radioactivity
Study
rabbitn: not reported in source
Comparator
Control formulation (same formula as Syntocinon)
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
Dose not stated · intranasalAs given in this study (rabbit).
Measurements
AUCt ratio (whole brain)
3.6 fold
TTA-121 vs control formulation
Source sentences
Summary
The area under the concentration-time curve to the time of the last quantifiable concentration (AUCt) in the whole brain was 3.6-fold higher in the [3H]TTA-121 group than in the [3H]CF group, indicating increased delivery of radioactivity to the brain by TTA-121 than by CF.
1 context sentence(design, population, supporting numbers)
Summary · context
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 3H-labeled oxytocin formulations-[3H]TTA-121 and [3H]CF were examined and compared.
Show in the study text Report a problemFND-3492900301
02AnimalAnimal study (in vivo)Pharmacokinetics
In rabbits given intranasal 3H-oxytocin, radioactivity distribution did not differ notably between the olfactory bulb and trigeminal nerve, which suggests transfer to the brain by both pathways.
In plain wordsIn rabbits, nasal oxytocin radioactivity reached the olfactory bulb and trigeminal nerve to a similar degree, which suggests two routes to the brain.
Peptide
Oxytocin
Outcome
No significant changeRadioactivity in olfactory bulb versus trigeminal nerve
Study
rabbitn: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
Dose not stated · intranasalAs given in this study (rabbit).
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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 3H-labeled oxytocin formulations-[3H]TTA-121 and [3H]CF were examined and compared.
Show in the study text Report a problemFND-3492900302
03AnimalAnimal study (in vivo)Pharmacokinetics
In rabbits given intranasal 3H-oxytocin, radioactivity increased in the prefrontal area and the precuneus.
In plain wordsIn rabbits, nasal oxytocin radioactivity increased in the prefrontal area and the precuneus, brain regions linked to oxytocin action in human imaging studies.
Peptide
Oxytocin
Outcome
IncreaseRadioactivity in prefrontal area and precuneus
Study
rabbitn: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
Dose not stated · intranasalAs given in this study (rabbit).
Source sentences
Summary
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.
1 context sentence(design, population, supporting numbers)
Summary · context
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 3H-labeled oxytocin formulations-[3H]TTA-121 and [3H]CF were examined and compared.
Show in the study text Report a problemFND-3492900303

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Version history

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Version 2Current
11 Oct 2026, 00:50 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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