CTP-692 is a deuterated form of D-serine
, an endogenous, required co-agonist of the N-methyl-D-aspartate (NDMA) receptor.
In a recent large, multicenter study, low dosage D-serine
(~30 mg/kg/d) did not separate from placebo, (33) but an open-label study suggests increased efficacy with dosages >30 mg/kg/d.
And an analogue of d-serine
, d-cycloserine "is also active at the glycine co-agonist site of NMDA receptors.
Led by Jose Feijo, group leader at the Instituto Gulbenkian de Ciencia (IGC), Portugal, and professor at Lisbon University, this international team has now discovered that the oscillations of calcium ions in the growing pollen tubes of tobacco and the weed Arabidopsis are facilitated by channels called Glutamate receptors-like (GLRs), and that these channels are opened by, amongst other components, a rare aminoacid, D-serine
helps promote long-term potentiation (LTP)--the strengthening of synaptic connections associated with learning and memory.
Among them are the immuno-histo-chemical study of D-serine
, preparing a polyclonal antiserum against D-asparte, inducing muscle contraction in silkworm larva with D-glutamic acid, a primary study of the D-amino acid accumulation system, whether D-amino acids are prevalent among eukaryotes, evaluating their nutrition, and determining D-amino acids in food and beverages using gas chromatography.
Serine is a required component in the biosynthesis of purines and pyrimidines, as well as an indispensable precursor for the synthesis of the amino acids glycine, cysteine and D-serine
antagonized phencyclidine- and MK-801-induced stereotyped behavior and ataxia.
In humans, D-serine
is thought to be an endogenous modulator for the NMDA receptor in various neuropsychiatric functions such as learning and nociception and has been implicated in pathological conditions such as schizophrenia and Alzheimer disease (1, 2, 5, 6).
Johns Hopkins University (Baltimore, MD) has patented high levels of D-serine
occur in mammalian brain, where it appears to be an endogenous ligand of the "glycine site" of NMDA receptors.
Further, the use of NMDAR glycine site agonists such as glycine, D-serine
, or D-cycloserine in clinical trials has demonstrated some efficacy in ameliorating the negative symptoms and cognitive disabilities in schizophrenics (Coyle and Tsai 2004a, 2004b).
The ability to grow in the presence of glycopeptides results from the change of the C-terminal residue of peptidoglycan precursors (D-Ala) to D-lactate (VanA, VanB, and VanD phenotypes) (6,7) or D-serine
(VanC, VanE, and VanG phenotypes) (8-10).