NDLI: Pharmacokinetics and cerebral distribution of glycine administered to rats

Content Provider	Springer Nature Link
Author	Kawai, buhiro Bannai, Makoto Seki, Shibu Koizumi, Tomori Shinkai, Kenji Nagao, Kenji Matsuzawa, Daisuke Takahashi, Michio Shimizu, Eiji
Copyright Year	2011
Abstract	High doses of glycine have been reported to improve negative schizophrenic symptoms, suggesting that ingested glycine activates glutamatergic transmission via N-methyl-d-aspartate (NMDA) receptors. However, the pharmacokinetics of administered glycine in the brain has not been evaluated. In the present study, the time- and dose-dependent distributions of administered glycine were investigated from a pharmacokinetic viewpoint. Whole-body autoradiography of radiolabeled glycine was performed, and time–concentration curves for glycine and serine in plasma, cerebrospinal fluid (CSF), and brain tissues were obtained. Furthermore, pharmacokinetic parameters were calculated. For a more detailed analysis, the amount of glycine uptake in the brain was evaluated using the brain uptake index method. Radiolabeled glycine was distributed among periventricular organs in the brain. Oral administration of 2 g/kg of glycine significantly elevated the CSF glycine concentration above the ED50 value for NMDA receptors. The glycine levels in CSF were 100 times lower than those in plasma. Glycine levels were elevated in brain tissue, but with a slower time-course than in CSF. Serine, a major metabolite of glycine, was elevated in plasma, CSF, and brain tissue. Glycine uptake in brain tissue increased in a dose-dependent manner. Time–concentration curves revealed that glycine was most likely transported via the blood–CSF barrier and activated NMDA receptors adjacent to the ventricles. The pharmacokinetic analysis and the brain uptake index for glycine suggested that glycine was transported into brain tissue by passive diffusion. These results provide further insight into the potential therapeutic applications of glycine.
Starting Page	2129
Ending Page	2137
Page Count	9
File Format	PDF
ISSN	09394451
Journal	Amino Acids
Volume Number	42
Issue Number	6
e-ISSN	14382199
Language	English
Publisher	Springer Vienna
Publisher Date	2011-06-07
Publisher Place	Vienna
Access Restriction	Subscribed
Subject Keyword	Brain uptake index Glycine Schizophrenia NMDA receptor Blood–CSF barrier Serine Biochemical Engineering Analytical Chemistry Biochemistry Proteomics Life Sciences Neurobiology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Biochemistry Clinical Biochemistry

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