IV glycine and oral -cycloserine effects on plasma and CSF amino acids in healthy humans

Background: The amino acid glycine, modulates neurotransmission via actions at GLY-A receptor and GLY-B receptor. The latter are coagonist sites associated with N-Methyl- -Aspartate (NMDA) glutamate receptors. The central bioavailability of peripherally administered glycine has not been adequately characterized in humans. Methods: Healthy human subjects were administered either oral -cycloserine (50 mg or placebo) and intravenous glycine (saline, 100 mg/kg or 200 mg/kg) in random order over 4 test days under double-blind conditions. Cerebrospinal fluid was collected by lumbar puncture performed on the first test day was analyzed to determine amino acid levels. The acoustic startle response was measured on the second test day. Results: Intravenous glycine dose-dependently increased both serum and CSF glycine and serine levels. Neither glycine nor DCS produced any significant effects on behavior, cognition or the acoustic startle response. Neither IV glycine nor DCS were associated with any toxicity. Conclusions: Thus, peripheral glycine administration raised CSF glycine levels without producing any clear central nervous system effects. Glycine and -cycloserine did not worsen cognitive test performance and did not induce behavioral symptoms on their own. The possibility that glycine and -cycloserine enhanced cognitive test performance cannot be excluded given the psychometric limitations of the test battery.