Haloperidol-induced cell death--mechanism and protection with vitamin E in vitro.
Haloperidol, a dopamine receptor antagonist and sigma-receptor-active neuroleptic drug, is cytotoxic to primary hippocampal neurones, C6 glioma cells and NCB20 cells. A 24 h challenge of these cells with haloperidol resulted in reduced cell viability and ultimately cell lysis. The most dramatic changes in cellular morphology were the retraction of cellular extensions, development of membrane blebs, and finally cell detachment from the culture dish. DNA isolated from haloperidol-treated cells was randomly degraded, indicating a necrotic rather than an apoptotic pathway of cell death. Vitamin E (alpha-tocopherol), a lipophilic free radical scavenger, prevented haloperidol-induced DNA fragmentation and ultimately cell death. These findings suggest that haloperidol induces necrotic cell death in which free radicals play a major role.
Behl
C
C
Max Planck Institute of Psychiatry, Clinical Institute, Munich, Germany.
Rupprecht
R
R
Skutella
T
T
Holsboer
F
F
D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D018492:Dopamine Antagonists / Q000633:toxicity*; D005910:Glioma; D006220:Haloperidol / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D006822:Hybrid Cells; D051379:Mice; D009336:Necrosis; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000494:pharmacology*
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D018696:Neuroprotective Agents; D014810:Vitamin E; D006220:Haloperidol