Short-term tropisetron treatment and cognitive and P50 auditory gating deficits in schizophrenia

Am J Psychiatry. 2012 Sep;169(9):974-81. doi: 10.1176/appi.ajp.2012.11081289.


Objective: The α7 nicotinic acetylcholine receptor (nAChR) is associated with cognitive and P50 auditory gating deficits in schizophrenia, and α7 nAChR agonists can potentially reverse these deficits. The authors examined multiple dosages of tropisetron, a partial agonist at the nAChR, for short-term effects on cognition and P50 deficits in schizophrenia.

Method: In a randomized double-blind design, 40 nonsmoking patients with schizophrenia who had P50 ratios greater than 0.5 and were stabilized on 3-6 mg/day of risperidone were randomly assigned to receive placebo (N=10) or oral tropisetron at 5 mg/day (N=10), 10 mg/day (N=10), or 20 mg/day (N=10). The authors measured P50 inhibitory gating and administered the Chinese-language version of the Repeatable Battery for the Assessment of Neuropsychological Status at baseline and after 10 days of treatment.

Results: After 10 days of treatment, all three daily doses of tropisetron significantly improved overall cognitive deficits, with 10 mg showing the greatest improvement for the immediate memory index score and 20 mg for the delayed memory index score on the cognitive battery. The P50 deficits were also improved, and that improvement was significantly correlated with cognitive improvement. Two patients in the 20 mg/day group dropped out because of adverse effects, but the other dosages were well tolerated.

Conclusions: The improvement of cognition with tropisetron appeared to be associated with normalization in P50 deficits. Thus, α7 nAChR agonists appear to be a promising therapeutic approach for the treatment of cognitive deficits that are related to abnormal P50 suppression in schizophrenia.

Trial registration: NCT00435370.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Auditory Perceptual Disorders / drug therapy*
  • Auditory Perceptual Disorders / physiopathology
  • Cognition Disorders / complications
  • Cognition Disorders / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Evoked Potentials, Auditory / drug effects
  • Evoked Potentials, Auditory / physiology
  • Female
  • Humans
  • Indoles / adverse effects
  • Indoles / pharmacology*
  • Indoles / therapeutic use
  • Male
  • Middle Aged
  • Neuropsychological Tests / statistics & numerical data
  • Nicotinic Agonists / pharmacology*
  • Nicotinic Agonists / therapeutic use
  • Receptors, Nicotinic / physiology
  • Schizophrenia / complications
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology
  • Schizophrenic Psychology*
  • Sensory Gating / drug effects*
  • Sensory Gating / physiology
  • Tropisetron
  • alpha7 Nicotinic Acetylcholine Receptor


  • Chrna7 protein, human
  • Indoles
  • Nicotinic Agonists
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • Tropisetron

Associated data