Archives of Pharmacal Research

, Volume 26, Issue 11, pp 951–959

Differential effects of typical and atypical neuroleptics on mitochondrial functionin vitro

  • Josephine S. Modica-Napolitano
  • Christopher J. Lagace
  • William A. Brennan
  • June R. Aprille
Research Articles Articles

DOI: 10.1007/BF02980205

Cite this article as:
Modica-Napolitano, J.S., Lagace, C.J., Brennan, W.A. et al. Arch Pharm Res (2003) 26: 951. doi:10.1007/BF02980205


A series of typical (chlorpromazine, haloperidol and thioridazine) and atypical (risperidone, quetiapine, clozapine and olanzapine) antipsychotics were tested for effects on integrated bioenergetic functions of isolated rat liver mitochondria. Polarographic measurement of oxygen consumption in freshly isolated mitochondria showed that electron transfer activity at respiratory complex I is inhibited by chlorpromazine, haloperidol, risperidone, and quetiapine, but not by clozapine, olanzapine, or thioridazine. Chlorpromazine and thioridazine act as modest uncouplers of oxidative phosphorylation. The typical neuroleptics inhibited NADH-coenzyme Q reductase in freeze-thawed mitochondria, which is a direct measure of complex I enzyme activity. The inhibition of NADH-coenzyme Q reductase activity by the atypicals risperidone and quetiapine was 2-4 fold less than that for the typical neuroleptics. Clozapine and olanzapine had only slight effects on NADH-coenzyme Q reductase activity, even at 200 μM. The relative potencies of these neuroleptic drugs as inhibitors of mitochondrial bioenergetic function is similar to their relative potencies as risk factors in the reported incidence of extrapyramidal symptoms, including tardive dyskinesia (TD). This suggests that compromised bioenergetic function may be involved in the cellular pathology underlying TD.

Key words

Neuroleptics Mitochondrial bioenergetic function Extrapyramidal symptoms Tardive dyskinesia Electron transport Respiratory enzyme complex I Oxidative phosphorylation 

Copyright information

© The Pharmaceutical Society of Korea 2003

Authors and Affiliations

  • Josephine S. Modica-Napolitano
    • 1
  • Christopher J. Lagace
    • 2
  • William A. Brennan
    • 3
  • June R. Aprille
    • 4
  1. 1.Department of BiologyMerrimack CollegeNorth AndoverUSA
  2. 2.Tufts University School of MedicineBostonUSA
  3. 3.Augusta Mental Health InstituteAugustaUSA
  4. 4.Department of BiologyUniversity of RichmondRichmondUSA
  5. 5.Maryland Hall 206University of RichmondRichmondUSA

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