Evaluation of Direct Transport Pathways of Glycine Receptor Antagonists and an Angiotensin Antagonist from the Nasal Cavity to the Central Nervous System in the Rat Model

Abstract

Intranasal administration resulted in greater delivery of the model drugs to the olfactory lobes and brain as compared to intravenous dosing. It is proposed that the drug moved through the neuro-olfactory system, primarily via paracellular pathways.

Intranasal Administration of Milnacipran in Rats: Evaluation of the Transport of Drugs to the Systemic Circulation and Central Nervous System and the Pharmacological Effect

“…administration, and it has been demonstrated by autoradiography that drugs administered intranasally are transferred to the brain and the CSF via the olfactory pathway. 33) Their results corresponded with our results in this study. They have also indicated that the three glycine receptor antagonists were transported to the CNS to differing degrees although they had similar molecular structures and similar physicochemical characteristics (DTP 51.95-99.99%).…”

Effects of Localized Hydrophilic Mannitol and Hydrophobic Nelfinavir Administration Targeted to Olfactory Epithelium on Brain Distribution

“…In contrast, the nose drops at the volumes used in this study (<30 μl) deposited at of the respiratory region. Our preliminary studies with 7-and 15-mm catheters for deposition to the olfactory region also showed much lower fraction of drug deposited at the olfactory region [even though this method has been used in many studies with the objective of targeting the olfactory region (11,(25)(26)(27)]. With catheter administration, the dye was localized to the distance that the catheter was inserted, but the dye did not penetrate the tight spaces between the nasal septum and the turbinates of the olfactory region well (data not shown).…”

Intranasal Administration as a Route for Drug Delivery to the Brain: Evidence for a Unique Pathway for Albumin

“…This explanation is supported by findings that elevated CSF levels of i.n. administered substances precede elevations in tissue levels (Charlton et al, 2008).…”

“…These patterns differ from those seen after i.n. administration of other peptides, including pituitary adenylate cyclase-activating polypeptide (Nonaka et al, 2012), the angiotensin antagonist GR138950 (1-[[3-bromo-2-[2-[[(trifluoromethyl) (Charlton et al, 2008), and testosterone (Banks et al, 2009). This variability could suggest that different molecules may undergo unique mechanisms of uptake.…”