Drug targeting to the brain : transfer of picolinic acid along the olfactory pathways
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.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2002 |
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| Erschienen: |
2002 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Journal of drug targeting - 10(2002), 6 vom: 28. Sept., Seite 469-78 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bergström, U [VerfasserIn] |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 16.04.2003 Date Revised 06.11.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM123531845 |
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| 100 | 1 | |a Bergström, U |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Drug targeting to the brain |b transfer of picolinic acid along the olfactory pathways |
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| 500 | |a Date Completed 16.04.2003 | ||
| 500 | |a Date Revised 06.11.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a picolinic acid |2 NLM | |
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| 700 | 1 | |a Franzén, A |e verfasserin |4 aut | |
| 700 | 1 | |a Eriksson, C |e verfasserin |4 aut | |
| 700 | 1 | |a Lindh, C |e verfasserin |4 aut | |
| 700 | 1 | |a Brittebo, E B |e verfasserin |4 aut | |
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