D-serine adjuvant treatment alleviates behavioural and motor symptoms in Parkinson's disease

Int J Neuropsychopharmacol. 2012 May;15(4):543-9. doi: 10.1017/S1461145711001015. Epub 2011 Jul 7.


Parkinson's disease (PD) manifestations include motor symptoms and behavioural deficits that resemble schizophrenia negative symptoms. The N-methyl-D-aspartate subtype of glutamate receptor (NMDAR) represents a novel pharmacological target in PD. D-serine (DSR) allosterically modulates in-vivo NMDAR-mediated neurotransmission and has been shown to improve negative and antipsychotic drug-induced parkinsonian symptoms in schizophrenia patients. This pilot study assessed DSR effects in ten PD patients who completed a 6-wk double-blind, placebo-controlled, crossover adjuvant treatment trial with 30 mg/kg.d DSR. Primary outcome analyses consisted of separate repeated-measures multivariate analyses of variance for Unified Parkinson's Disease Rating Scale (UPDRS), Simpson-Angus Scale for Extrapyramidal Symptoms (SAS), Abnormal Involuntary Movement Scale (AIMS), and Positive and Negative Syndrome Scale (PANSS) scores. DSR treatment was well tolerated and resulted in increased DSR serum levels (p=0.001) and significantly reduced UPDRS (p=0.02), SAS (p=0.009) and PANSS (0.05) total scores. These preliminary findings suggest that DSR treatment may be beneficial in PD. Larger-sized studies with optimized DSR dosages are warranted.

Trial registration: ClinicalTrials.gov NCT00215904.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antipsychotic Agents / blood
  • Antipsychotic Agents / therapeutic use*
  • Behavioral Symptoms / drug therapy*
  • Behavioral Symptoms / etiology*
  • Cross-Sectional Studies
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Movement / drug effects*
  • Parkinson Disease / blood
  • Parkinson Disease / complications*
  • Parkinson Disease / drug therapy
  • Psychiatric Status Rating Scales
  • Serine / blood
  • Serine / therapeutic use*
  • Severity of Illness Index


  • Antipsychotic Agents
  • Serine

Associated data

  • ClinicalTrials.gov/NCT00215904