D-Cycloserine in Neuropsychiatric Diseases: A Systematic Review

Abstract

D-Cycloserine, known from tuberculosis therapy, has been widely introduced to neuropsychiatric studies, since its central active mechanism as a partial NMDA-agonist has been found. In this review, we evaluate its therapeutic potential in neuropsychological disorders and discuss its pitfalls in terms of dosing and application frequency as well as its safety in low-dose therapy. Therefore, we identified 91 clinical trials by performing a Medline search. We demonstrate in part preliminary but increasing evidence that D-cycloserine may be effective in various psychiatric diseases, including schizophrenia, anxiety disorders, addiction, eating disorders, major depression, and autism as well as in neurological diseases, including dementia, Alzheimer's disease, and spinocerebellar degeneration. D-Cycloserine in low-dose therapy is safe, but there is still a need for new drugs with higher specificity to the different N-methyl-D-aspartate-receptor subunits.

Figure 1.

Schematic structure of the NMDA receptor. The NMDA receptor consists of 2 subunits (NR1 and NR2A, NR2B or NR2C). The NR2 subunits hold the glutamate binding site (GluBS), where the main agonist glutamate (Glu) binds. The NR1 subunit holds the glycine binding site (GlyBS), where the natural co-agonist glycine (Gly) or the partial agonist D-Cycloserine (DCS) bind. For further agonists and antagonists of the GlyBS see Table 1. For further details on the structure of the NMDA receptor see Dravid et al. (2010).