Abstract
3-Hydroxycyclopent-1-enecarboxylic acid (HOCPCA, 1) is a potent ligand for the high-affinity GHB binding sites in the CNS. An improved synthesis of 1 together with a very efficient synthesis of [(3)H]-1 is described. The radiosynthesis employs in situ generated lithium trimethoxyborotritide. Screening of 1 against different CNS targets establishes a high selectivity, and we demonstrate in vivo brain penetration. In vitro characterization of [(3)H]-1 binding shows high specificity to the high-affinity GHB binding sites.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzocycloheptenes / chemistry
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Benzocycloheptenes / metabolism
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Binding Sites
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Binding, Competitive
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Brain / metabolism
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Carboxylic Acids / chemical synthesis
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Carboxylic Acids / chemistry
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Carboxylic Acids / metabolism*
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Cell Line
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Central Nervous System / metabolism*
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Cyclopentanes / chemical synthesis
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Cyclopentanes / chemistry
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Cyclopentanes / metabolism*
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Drug Stability
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Hydroxybutyrates / chemistry
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Hydroxybutyrates / metabolism*
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Kinetics
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Ligands
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Male
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Models, Chemical
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Molecular Structure
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
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Synaptic Membranes / metabolism
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Tritium / metabolism
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gamma-Aminobutyric Acid / chemistry
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gamma-Aminobutyric Acid / metabolism
Substances
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3-hydroxycyclopent-1-enecarboxylic acid
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Benzocycloheptenes
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Carboxylic Acids
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Cyclopentanes
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Hydroxybutyrates
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Ligands
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Tritium
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NCS 382
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4-hydroxybutyric acid
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gamma-Aminobutyric Acid