Sigma receptor-active neuroleptics are cytotoxic to C6 glioma cells in culture.
When exposed to neuroleptics (100 microM), C6 glioma cells exhibited marked changes in cell morphology, accompanied by cessation of cell division and ultimately cell death. The degree of activity generally correlated with binding affinity at sigma sites: fluphenazine = perphenazine = haloperidol = reduced haloperidol > pimozide = spiperone >> >> (-)-sulpiride. Sigma-inactive compounds (100 microM) which block dopamine, serotonin, phencyclidine, muscarinic receptors and adrenoceptors showed no effect. These results may suggest a role of sigma binding sites in maintenance of cell viability.
Vilner
B J
BJ
Unit on Receptor Biochemistry and Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892.
Bowen
W D
WD
D014150:Antipsychotic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005910:Glioma / Q000473:pathology*; D006801:Humans; D017465:Receptors, Opioid, delta / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D014150:Antipsychotic Agents; D017465:Receptors, Opioid, delta