Abstract |
(S)-2-ethyl-7-fluoro-3-oxo-3, 4-dihydro-2H-quinoxaline-carboxylic acid isopropylester ( GW420867X) inhibits HIV-1 reverse transcriptase and could be used for the treatment of HIV infection. This study quantified the movement of [14C] GW420867X into the CNS by means of a guinea-pig brain perfusion technique. Results indicated that [14C] GW420867X can enter the brain (Kin: 38.4+/-7.7 microl min(-1) g(-1)) and cerebrospinal fluid (CSF; Kin: 1.2+/-0.1 microl min(-1) g(-1)). Self-inhibition studies also suggested the presence of a saturable transport system for [14C] GW420867X at the blood-brain barrier (BBB). Thus [14C] GW420867X can enter the brain via the BBB and, compared with the blood-CSF barrier, this route is the predominant pathway for the brain entry of this drug. This would suggest that GW420867X is a promising drug for the treatment of HIV infection within the brain.
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Authors | S Thomas, L Cass, W Prince, M Segal |
Journal | Neuroreport
(Neuroreport)
Vol. 11
Issue 17
Pg. 3811-5
(Nov 27 2000)
ISSN: 0959-4965 [Print] England |
PMID | 11117496
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- GW420867X
- Quinoxalines
- Reverse Transcriptase Inhibitors
- Mannitol
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Topics |
- Animals
- Blood-Brain Barrier
(physiology)
- Brain
(metabolism)
- Capillaries
(metabolism)
- Chemical Phenomena
- Chemistry, Physical
- Guinea Pigs
- Mannitol
(pharmacokinetics)
- Quinoxalines
(cerebrospinal fluid, chemistry, pharmacokinetics)
- Reverse Transcriptase Inhibitors
(cerebrospinal fluid, pharmacokinetics)
- Solubility
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