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Development of a high-throughput method for the determination of pharmacological levels of plasma D-serine.

Abstract
D-Serine administration has been shown to be effective for the treatment of schizophrenia symptoms. However, D-Serine must be administered at high doses to observe clinical effects. This is due in large part to D-Serine undergoing oxidation by D-Serine acid oxidase (DAAO) before it reaches the brain. Consequently, coadministration of D-Serine with a DAAO inhibitor has been suggested as a way to lower the dose of D-serine required to treat schizophrenia. During the characterization of DAAO inhibitors as potential drugs, inhibitors are evaluated in rodents for their ability to increase plasma D-Serine levels after oral coadministration. Current high-performance liquid chromatography (HPLC)-based methodologies to measure D-Serine in plasma are time-consuming and are not amenable to concomitant analysis of multiple samples. We report the characterization of a 96-well format assay to monitor D-Serine in plasma that greatly expedites analysis time. The assay involves the use of strong cation exchange solid phase extraction (SPE) to isolate D-Serine from plasma followed by quantitation of D-Serine using the DAAO-catalyzed reaction. Plasma D-Serine determination using this assay could also be used as pharmacodynamic marker and as biomarker.
AuthorsJesse Alt, Camilo Rojas, Krystyna Wozniak, Ying Wu, Dana Ferraris, Takashi Tsukamoto, Barbara Slusher
JournalAnalytical biochemistry (Anal Biochem) Vol. 419 Issue 2 Pg. 106-9 (Dec 15 2011) ISSN: 1096-0309 [Electronic] United States
PMID21889486 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2011 Elsevier Inc. All rights reserved.
Chemical References
  • Cation Exchange Resins
  • Enzyme Inhibitors
  • Serine
  • D-Amino-Acid Oxidase
Topics
  • Administration, Oral
  • Animals
  • Cation Exchange Resins
  • D-Amino-Acid Oxidase (antagonists & inhibitors, metabolism)
  • Enzyme Assays
  • Enzyme Inhibitors (administration & dosage, pharmacology)
  • High-Throughput Screening Assays (methods)
  • Mice
  • Reference Standards
  • Serine (blood, chemistry, isolation & purification)
  • Solid Phase Extraction

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