Neuroleptic treatment effect on mitochondrial electron transport chain: peripheral blood mononuclear cells analysis in psychotic patients.
A limitation in the use of classic neuroleptic drugs is the eventual appearance of extrapyramidal symptoms. Some studies, mainly based on experimental situations, have related these symptoms with a defect in the mitochondrial electron transport chain (ETC), especially with complex I (CI). One of the advantages of the "atypical" neuroleptics is a lower incidence of movement disorders. We studied peripheral blood mononuclear cells from naive schizophrenic patients (n = 25) and patients under chronic treatment with 1 "typical" neuroleptic (haloperidol, n = 15) or 1 "atypical" neuroleptic (risperidone, n = 23; or clozapine, n = 21). Patients were on standard clinical situation, on treatment for at least 28 months, and did not present signs or symptoms of extrapyramidal dysfunction. Absolute enzyme activities of ETC complexes I to IV were spectrophotometrically quantified, and oxygen consumption with substrates of different complexes was measured polarographically. As an indirect measure of oxidative damage, we quantified membrane lipid peroxidation through the loss of cis-parinaric acid fluorescence. We found differences among groups when comparing the activity of CI, which was decreased in patients receiving neuroleptics, either assessed enzymatically or through oxygen consumption. This effect was lower for atypical neuroleptics than for haloperidol. Haloperidol was also associated with a significant increase of peripheral blood mononuclear cell membrane peroxidation. We conclude that antipsychotics given at clinical standard doses, either typical or atypical, inhibit CI of the ETC. It remains to be established if this finding in a nontarget tissue for antipsychotics may account for the lower incidence of movement disorders observed in patients on atypical agents.
Casademont
Jordi
J
Muscle Research Unit, Internal Medicine Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain. jcasademont@santpau.es
Garrabou
Glòria
G
Miró
Oscar
O
López
Sònia
S
Pons
Alexandre
A
Bernardo
Miquel
M
Cardellach
Francesc
F
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D003024:Clozapine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D004579:Electron Transport / Q000187:drug effects; D042967:Electron Transport Complex I / Q000097:blood*; D005260:Female; D006220:Haloperidol / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009459:Neuroleptic Malignant Syndrome / Q000209:etiology; D018967:Risperidone / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D042967:Electron Transport Complex I; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone