NMDA agonists for autism spectrum disorders: progress and possibilities

Transgenic mice with NMDA-receptor (NMDAR) hypofunction display impaired sociability (i.e., diminished preference for exploring conspecifics), supporting a critical role for the NMDAR in regulation of sociability. The endogenous tone of NMDAR-mediated neurotransmission is altered in the Balb/c mouse model of autism spectrum disorders; thus, the effects of targeting the NMDAR in Balb/c mice on sociability, cognition and stereotypic behavior were explored. Positive effects of this pharmacotherapeutic strategy were observed in Balb/c and other relevant mouse strains displaying impaired sociability. Furthermore, in a preliminary translational clinical trial, D-cycloserine, a partial glycine B site agonist, improved sociability and diminished stereotypies in a sample of adolescents and young adults with autism spectrum disorders. The data encourage pharmacotherapeutic targeting of the NMDAR.