title: Pharmacokinetics and cerebral distribution of glycine administered to rats.
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.
authors.affiliation: Institute of Life Sciences, Ajinomoto Co., Inc, 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki-shi, Kanagawa, 210-8681, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kawai
authors.forename: Makoto
authors.initials: M
authors.lastname: Bannai
authors.forename: Shinobu
authors.initials: S
authors.lastname: Seki
authors.forename: Tomonori
authors.initials: T
authors.lastname: Koizumi
authors.forename: Kenji
authors.initials: K
authors.lastname: Shinkai
authors.forename: Kenji
authors.initials: K
authors.lastname: Nagao
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsuzawa
authors.forename: Michio
authors.initials: M
authors.lastname: Takahashi
authors.forename: Eiji
authors.initials: E
authors.lastname: Shimizu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001345:Autoradiography; D001682:Biological Availability; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism*; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D008297:Male; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012694:Serine / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D002250:Carbon Radioisotopes; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D005998:Glycine