Delivery of oxytocin to the brain for the treatment of autism spectrum disorder by nasal application
Abstract
Oxytocin (OXT) is a cyclic nonapeptide, two amino acids of which are cysteine, forming an intramolecular disulfide bond. OXT is produced in the hypothalamus and is secreted into the bloodstream from the posterior pituitary. As recent studies have suggested that OXT is a neurotransmitter exhibiting central effects important for social deficits, it has drawn much attention as a drug candidate for the treatment of autism. Although human-stage clinical trials of the nasal spray of OXT for the treatment of autism have already begun, few studies have examined the pharmacokinetics and brain distribution of OXT after nasal application. The aim of this study is to evaluate the disposition, nasal absorption, and therapeutic potential of OXT after nasal administration. The pharmacokinetics of OXT after intravenous bolus injection to rats followed a two-compartment model, with a rapid initial half-life of 3 min. The nasal bioavailability of OXT was approximately 2%. The brain concentration of OXT after nasal application was much higher than that after intravenous application, despite much lower concentrations in the plasma. More than 95% of OXT in the brain was directly transported from the nasal cavity. The in vivo stress-relief effect by OXT was observed only after intranasal administration. These results indicate that pharmacologically active OXT was effectively delivered to the brain after intranasal administration. In conclusion, the nasal cavity is a promising route for the efficient delivery of OXT to the brain.
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Intranasal oxytocin elevates brain-level presence of oxytocin.
“intranasal oxytocin elevates brain-level presence of oxytocin”
From Oxytocin promotes coordinated out-group attack during intergroup conflict in humans (2019) · cites this paper as Tanaka et al., 2018
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- Authors
- Tanaka, A., Furubayashi, T., Arai, M., Inoue, D., Kimura, S., Kiriyama, A., Kusamori, K., Katsumi, H., Yutani, R., Sakane, T., & Yamamoto, A.
- Affiliations
- Kyoto Pharmaceutical University (JP)
- Shujitsu University (JP)
- Doshisha Women's College of Liberal Arts (JP)
- Kobe Pharmaceutical University (JP)
- Corresponding author
- Sakane, Toshiyasu
- ORCID
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-01-16
- Volume
- 15
- Issue
- 3
- Pages
- 1105-1111
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- OpenAlex
- W2783569013
- Cited by
- 104
- References
- 50
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 11 · 2023: 15 · 2022: 13 · 2021: 17 · 2020: 12 · 2019: 9 · 2018: 9
- FWCI
- 5.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- oxytocin, autism spectrum disorder, intranasal administration, intranasal drug delivery, brain distribution, pharmacokinetics, nasal bioavailability, two-compartment model, stress reduction, social behavior
- MeSH terms
- Autism Spectrum Disorder, Administration, Intranasal, Animals, Behavior, Animal, Biological Availability, Brain, Disease Models, Animal, Humans, Injections, Intravenous, Male, Oxytocin, Stress, Psychological, Treatment Outcome, Rats, Wistar, Mice, Rats
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