Abstract
The 'NMDA hypofunction hypothesis of schizophrenia' can be tested in a number of ways. DAO is the enzyme primarily responsible for the metabolism of d-serine, a co-agonist for the NMDA receptor. We identified novel DAO inhibitors, in particular, acid 1, which demonstrated moderate potency for DAO in vitro and ex vivo, and raised plasma d-serine levels after dosing ip to rats. In parallel, analogues were prepared to survey the SARs of 1.
MeSH terms
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Animals
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Carboxylic Acids / chemical synthesis*
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Carboxylic Acids / chemistry
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Carboxylic Acids / pharmacology*
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Combinatorial Chemistry Techniques
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Crystallography, X-Ray
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D-Amino-Acid Oxidase / antagonists & inhibitors*
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Molecular Conformation
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Molecular Structure
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Pyrroles / chemical synthesis*
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Pyrroles / chemistry
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Pyrroles / pharmacology*
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Rats
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Schizophrenia / drug therapy
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Serine / analysis
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Serine / blood
Substances
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Carboxylic Acids
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Enzyme Inhibitors
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Pyrroles
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Serine
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D-Amino-Acid Oxidase