Evaluation of human D-amino acid oxidase inhibition by anti-psychotic drugs in vitro.

Abstract

It is of importance to determine whether antipsychotic drugs currently prescribed for schizophrenia exert D-amino acid oxidase (DAO)-inhibitory effects. We first investigated whether human (h)DAO can metabolize D-kynurenine (D-KYN) to produce the fluorescent compound kynurenic acid (KYNA) by using high-performance liquid chromatography with mass spectrometry, and fluorescence spectrometry. After confirmation of KYNA production from D-KYN by hDAO, 8 first- and second-generation antipsychotic drugs, and 6 drugs often prescribed concomitantly, were assayed for hDAO-inhibitory effects by using in vitro fluorometric methods with D-KYN as the substrate. DAO inhibitors 3-methylpyrazole-5-carboxylic acid and 4H-thieno[3,2-b]pyrrole-5-carboxylic acid inhibited KYNA production in a dose-dependent manner. Similarly, the second-generation antipsychotics blonanserin and risperidone were found to possess relatively strong hDAO-inhibitory effects in vitro (5.29 ± 0.47 μM and 4.70 ± 0.17 μM, respectively). With regard to blonanserin and risperidone, DAO-inhibitory effects should be taken into consideration in the context of their in vivo pharmacotherapeutic efficacy.

• Authors: Miho Shishikura, Hitomi Hakariya, Sumiko Iwasa, Takashi Yoshio, Hideaki Ichiba, Kazuko Yorita, Kiyoshi Fukui, Takeshi Fukushima
• Journal: Bioscience trends (Biosci Trends) Vol. 8 Issue 3 Pg. 149-54 (Jun 2014) ISSN: 1881-7823 [Electronic] Japan
• PMID: 25030849 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents
• Piperazines
• Piperidines
• blonanserin
• D-Amino-Acid Oxidase
• Risperidone

Topics

• Antipsychotic Agents (pharmacology)
• D-Amino-Acid Oxidase (metabolism)
• Enzyme Activation (drug effects)
• Humans
• Piperazines (pharmacology)
• Piperidines (pharmacology)
• Risperidone (pharmacology)