The glycine/NMDA receptor ligand (+)-HA-966 but not D-cycloserine has potent antidystonic efficacy in a genetic animal model of dystonia.

The effects of R-(+)-HA-966 ((+)-3-amino-1-hydroxypyrrolid-2-one), a low-efficacy partial agonist of the glycine modulatory site of the NMDA receptor complex, were studied in an inbred line of Syrian golden hamsters with generalized dystonia, a frequent movement disorder in humans. The effects of R-(+)-HA-966 were compared with those of D-cycloserine, a glycine/NMDA receptor ligand with higher intrinsic activity. R-(+)-HA-966, 30-60 mg/kg i.p., potently reduced the severity of dystonic attacks in the mutant hamster model of dystonia without inducing any behavioural adverse effects. D-Cycloserine did not exert antidystonic activity at i.p. doses of 10-40 mg/kg, which might be due to its much higher intrinsic activity at the glycine site. The data indicate that the antidystonic effect of (+)-HA-966 is related to antagonism of NMDA receptor-mediated excitatory neurotransmission.