Peripherally administered reduced pterins do enter the brain.

G Kapatos; S Kaufman

doi:10.1126/science.7233193

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PubMed · 7233193

Peripherally administered reduced pterins do enter the brain.

G Kapatos·S Kaufman

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Abstract

The content of tetrahydrobiopterin in rat brain was doubled by peripherally administered tetrahydrobiopterin, with the natural 1 diastereoisomer more effective than the unnatural d configuration. The model pteridine, 6-methyltetrahydropterin was ten times more efficient than tetrahydrobiopterin in crossing the blood-brain barrier, and striatal concentrations of 6-methyltetrahydropterin remained elevated for 2 hours, declining with a half-life of 3 hours. While no evidence for a specific uptake mechanism for concentrating 6-methyltetrahydropterin in cells containing tetrahydrobiopterin was detected, the pterin was found in ts presumed site of action, the nerve terminal. Replacement therapy with reduced pterins may therefore be effective in the treatment of the neurological disorders associated with the variant forms of hyperphenylalaninemia that result from defects in the biosynthesis or metabolism of tetrahydrobiopterin within the central nervous system.

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Animals Biopterins Blood-Brain Barrier Brain Male Pteridines Pterins Rats Stereoisomerism Structure-Activity Relationship Journal Article

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G Kapatos, S Kaufman. 1981-05-22. Peripherally administered reduced pterins do enter the brain.. https://doi.org/10.1126/science.7233193

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