| ironjustice@aol.com 2006-06-04, 9:21 am |
| Drug targeting to the brain: transfer of picolinic acid along the
olfactory pathways.
Bergstr=F6m U, Franz=E9n A, Eriksson C, Lindh C, Brittebo EB
J Drug Target. 2002 Sep ; 10(6): 469-78
Picolinic acid (PA) protects against quinolinic acid- and kainic
acid-induced neurotoxicity in the brain. To study the uptake of PA to
the brain, we administered [3H]PA via a unilateral nasal instillation
or iv injection to mice. Autoradiography demonstrated a rapid uptake of
radioactivity in the olfactory nerve layer and in the ipsilateral
olfactory bulb (OB) following nasal instillation of [3H]PA. After 4 h,
there was a high level of radioactivity in the central parts of the
ipsilateral OB and olfactory peduncle. Moreover, iv injection of [3H]PA
demonstrated a selective uptake and retention of radioactivity in the
OB. Gas chromatography-mass spectrometry (GC-MS) demonstrated the
presence of PA and PA-glycine conjugate in the OB. In mice with reduced
peripheral olfactory innervations there was a decreased uptake of
[3H]PA in the OB as compared to controls suggesting that an intact
olfactory neuroepithelium is a prerequisite for an uptake of PA to the
OB. There is an increased interest in brain targeting of drugs with
limited ability to pass the blood-brain barrier. The present results
demonstrate that PA fulfils structural requirements for a transfer
along the olfactory pathways to the brain.
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