Drug transport into the mammalian brain: the nasal pathway and its specific metabolic barrier.
It is generally accepted that the rate of entry into and distribution of drugs and other xenobiotics within the central nervous system (CNS) depends on the particular anatomy of the brain microvessels forming the blood-brain barrier (BBB), and of the choroid plexus forming the blood-cerebrospinal fluid barrier (CSF), which possess tight junctions preventing the passage of most polar substances. Drug entry to the CNS also depends on the physicochemical properties of the substances, which can be metabolised during this transport to pharmacologically inactive, non-penetrating polar products. Finally, the entry of drugs may be prevented by multiple complex specialized carriers, which are able to catalyse the active transport of numerous drugs and xenobiotics out of the CNS. Nasal delivery is currently considered as an efficient tool for systemic administration of drugs that are poorly absorbed via the oral route, and increasing evidence suggests that numerous drugs and potentially toxic xenobiotics can reach the CNS by this route. This short review summarizes recent knowledge on factors controlling the nasal pathway, focusing on drug metabolising enzymes in olfactory mucosa, olfactory bulb and brain, which should constitute a CNS metabolic barrier.
Minn
Alain
A
Laboratoire de Pharmacologie, UMR No 7561 CNRS-Université Henri-Poincaré-Nancy 1, Faculté de Médecine, Vandoeuvre-lès-Nancy, France. minn@medecine.uhp-nancy.fr
Leclerc
Séverine
S
Heydel
Jean-Marie
JM
Minn
Anne-Laure
AL
Denizcot
Claire
C
Cattarelli
Martine
M
Netter
Patrick
P
Gradinaru
Daniela
D
D000281:Administration, Intranasal; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D006801:Humans; D009296:Nasal Cavity / Q000187:drug effects / Q000378:metabolism*