No abstract

No abstract

No abstract

No abstract

No 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.

No abstract

The aim of the present study has been to confirm the existence of a transport pathway for a drug (cephalexin) to the cerebrospinal fluid (CSF) directly from the nasal cavity, by comparing the drug's concentrations in CSF after intranasal (i.n.), intravenous (i.v.) and intraduodenal (i.d.) administration. Higher levels of the drug were found in CSF following i.n. administration compared with the i.v. and i.d. routes, even though its plasma concentrations were similar. These findings suggest the existence of a direct transport pathway for cephalexin from the nasal cavity to the CSF. The concentration of drug in CSF at 15 min after i.n. administration was higher than that at 30 min. In contrast, its concentrations in CSF at 15 min after i.v. and i.d. administration were not significantly different from those at 30 min. The results confirm the presence of a direct transport pathway to CSF from the nasal cavity. This pathway may represent a new delivery route to CSF and possibly to brain parenchyma.