Y-931, a novel atypical antipsychotic drug, is less sensitive to oxidative phenomena.
The oxidation behavior of Y-931, a potent atypical antipsychotic drug, was compared with that of clozapine and olanzapine. In two enzymatic systems (horseradish peroxidase (HRP)/glutathione (GSH) and HRP/H(2)O(2)/GSH) which generate thiyl radicals, clozapine markedly strengthened the electron paramagnetic resonance (EPR) signal for the radical. Olanzapine, Y-931 and the major metabolites (compounds 1-3) had no or minimal effect on the intensity of this signal. In addition, the redox potential values for the three derivatives were in accord with the EPR spin trapping results. In toxicological experiments in human leukocytes, a concentration-dependent toxicity was observed when neutrophils were incubated with clozapine (1-10 micromol/l) and H(2)O(2) (1 mmol/l). However, Y-931 and olanzapine did not show remarkable toxicity under the conditions.
Kohara
Toshiyuki
T
Exploratory Research I (CNS), Pharmaceuticals Research Division, Mitsubishi Pharma Corporation, Iruma, Saitama, Japan. Kohara.Toshiyuki@mh.m-pharma.co.jp
Koyama
Toshiki
T
Fujimura
Masatake
M
Tanaka
Hiroshi
H
Maeda
Junichi
J
Fujimoto
Tetsuya
T
Yamamoto
Iwao
I
Arita
Masafumi
M
D014150:Antipsychotic Agents / Q000378:metabolism* / Q000494:pharmacology; D001569:Benzodiazepines / Q000378:metabolism* / Q000494:pharmacology; D003024:Clozapine / Q000378:metabolism* / Q000494:pharmacology; D004355:Drug Stability; D005978:Glutathione / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide; D009504:Neutrophils / Q000187:drug effects; D000077152:Olanzapine; D010084:Oxidation-Reduction; D010879:Piperazines / Q000378:metabolism* / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
C434584:8-fluoro-12-(4-methylpiperazin-1-yl)-6H-(1)benzothieno(2,3-b)(1,5)benzodiazepine; D014150:Antipsychotic Agents; D010879:Piperazines; D001569:Benzodiazepines; D010890:Pirenzepine; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D005978:Glutathione; D003024:Clozapine; D000077152:Olanzapine