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Drug targeting to the brain: Transfer of picolinic acid along the olfactory pathways

Bergstrom, U; Franzen, A; Eriksson, C; Lindh, Christian LU and Brittebo, EB (2002) In Journal of Drug Targeting 10(6). p.469-478
Abstract
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 [H-3]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 [H-3]PA. After 4h, there was a high level of radioactivity in the central parts of the ipsilateral OB and olfactory peduncle. Moreover, iv injection of [H-3]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... (More)
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 [H-3]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 [H-3]PA. After 4h, there was a high level of radioactivity in the central parts of the ipsilateral OB and olfactory peduncle. Moreover, iv injection of [H-3]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 [H-3]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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
olfactory system, picolinic acid, intranasal instillation, autoradiography
in
Journal of Drug Targeting
volume
10
issue
6
pages
469 - 478
publisher
Taylor & Francis
external identifiers
  • pmid:12575737
  • wos:000178945600005
  • scopus:0036709519
ISSN
1061-186X
DOI
10.1080/1061186021000038346
language
English
LU publication?
yes
id
79bbf7cd-0365-4e00-8cc8-ae2c82e1e77e (old id 324467)
date added to LUP
2007-08-10 08:35:19
date last changed
2017-01-01 07:09:13
@article{79bbf7cd-0365-4e00-8cc8-ae2c82e1e77e,
  abstract     = {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 [H-3]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 [H-3]PA. After 4h, there was a high level of radioactivity in the central parts of the ipsilateral OB and olfactory peduncle. Moreover, iv injection of [H-3]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 [H-3]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.},
  author       = {Bergstrom, U and Franzen, A and Eriksson, C and Lindh, Christian and Brittebo, EB},
  issn         = {1061-186X},
  keyword      = {olfactory system,picolinic acid,intranasal instillation,autoradiography},
  language     = {eng},
  number       = {6},
  pages        = {469--478},
  publisher    = {Taylor & Francis},
  series       = {Journal of Drug Targeting},
  title        = {Drug targeting to the brain: Transfer of picolinic acid along the olfactory pathways},
  url          = {http://dx.doi.org/10.1080/1061186021000038346},
  volume       = {10},
  year         = {2002},
}