Abstract
The 4-methyl analogue of the potent inhibitor of CNS L-glutamate neurotransmitter transporters, L-trans-2,4-PDC, was synthesized via a 1,3-dipolar cycloaddition reaction sequence. The bioassays performed not only exhibit increased potency of the methylated derivative over L-trans-2,4-PDC, but also exhibit non-substrate properties at the rat forebrain synaptosomal glutamate transporter while the parent L-trans-2,4-PDC exhibits substrate properties. These results support two hypotheses developed for distinguishing the physiological properties of transport inhibitors based on molecular modeling studies, and are reported here.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Transport System X-AG / drug effects*
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Animals
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Carboxylic Acids / chemistry*
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Computational Biology
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Cyclization
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Dicarboxylic Acids*
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Excitatory Amino Acid Transporter 2 / chemistry
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Excitatory Amino Acid Transporter 2 / drug effects
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In Vitro Techniques
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Indicators and Reagents
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Kinetics
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Methylation
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Models, Chemical
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Models, Molecular
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Molecular Conformation
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Prosencephalon / metabolism
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Pyrrolidines / chemistry*
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Rats
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Synaptosomes / drug effects
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Synaptosomes / metabolism
Substances
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Amino Acid Transport System X-AG
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Carboxylic Acids
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Dicarboxylic Acids
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Excitatory Amino Acid Transporter 2
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Indicators and Reagents
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Pyrrolidines
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pyrrolidine-2,4-dicarboxylic acid