Antidepressant and antipsychotic drugs differentially affect PON1 enzyme activity

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 30; no. 2; pp. 245 - 249
• Main Authors: Avcikurt, Ayla Solmaz, Sinan, Selma, Kockar, Feray
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.04.2015; Informa Healthcare
• Subjects: Acepromazine - chemistry; Acepromazine - pharmacology; Antidepressant; Antidepressive Agents - chemistry; Antidepressive Agents - pharmacology; antipsychotic; Antipsychotic Agents - chemistry; Antipsychotic Agents - pharmacology; Aryldialkylphosphatase - antagonists & inhibitors; Aryldialkylphosphatase - blood; Aryldialkylphosphatase - isolation & purification; Diazepam - chemistry; Diazepam - pharmacology; Electrophoresis, Polyacrylamide Gel; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Female; Fluoxetine - chemistry; Fluoxetine - pharmacology; Haloperidol - chemistry; Haloperidol - pharmacology; Humans; inhibition; Kinetics; Molecular Structure; paraoxonase; purification; Antidepressant; inhibition; antipsychotic; paraoxonase; purification; IC50
• ISSN: 1475-6366; 1475-6374
• DOI: 10.3109/14756366.2014.913038

Abstract Human serum paraoxonase (PON1, EC 3.1.8.1.) is a high-density lipid (HDL)-associated, calcium-dependent enzyme. In this study, the effects of Haloperidol, Fluoxetine hydrochloride, Diazepam and Acepromazine drugs used for the therapy of antidepressant and antipsychotic diseases, on paraoxonase enzyme activity was studied in in vitro inhibition studies on purified human serum PON1. PON1 enzyme was purified from human blood using two-step procedures, namely, ammonium sulfate precipitation and sepharose-4B-l-tyrosine-1-napthylamine hydrophobic interaction chromatography. The overall purification of human serum PON1 was obtained in a activity of 109.29 U/mL and this enzyme was purified 125-fold. The SDS-polyacrylamide gel electrophoresis of the enzyme indicates a single band with an apparent MW of 43 kDa. Inhibition studies indicated that haloperidol and fluoxetine hydrocloride were effective inhibitors on purified human serum PON1 activity with IC50 of 0.187 and 3.08 mM values, respectively. The kinetics of interaction of haloperidol and fluoxetine hydrocloride with the purified human serum PON1 indicated uncompetitive inhibiton pattern with Ki of 4.15 and 0.007 mM, respectively.