Drug targeting to the brain: Transfer of picolinic acid along the olfactory pathways
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/324467
- author
- Bergstrom, U ; Franzen, A ; Eriksson, C ; Lindh, Christian LU and Brittebo, EB
- organization
- publishing date
- 2002
- 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
- 2016-04-01 16:35:04
- date last changed
- 2022-02-27 22:12:36
@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}}, keywords = {{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}}, doi = {{10.1080/1061186021000038346}}, volume = {{10}}, year = {{2002}}, }