In vitro effects of three antidepressant drugs on plasma paraoxonase activity
-
Mohamed Hachem Saadaoui
,
Ilhem Hellara
Abstract
Background: Paraoxonase 1 (PON1) is important in organophosphates and xenobiotic metabolism and as an antioxidant bio-scavenger. PON1 activity was shown to significantly decrease in depressed patients after antidepressant treatment instauration. Our aim was to investigate the in vitro inhibitory effects of three antidepressants (imipramine, amitriptyline and fluoxetine) on PON1 activity.
Methods: Plasma from healthy volunteers was spiked with antidepressant drugs. The working solutions were then diluted with plasma to obtain concentrations that covered the therapeutic margin. PON1 was tested by a kinetic method in triplicate after incubation at 37°C for 2 h.
Results: Tricyclic antidepressants significantly inhibited PON1. Fluoxetine had no effect. The inhibition percentage for imipramine was 15.6% at 100 μg/L after incubation for 1 h (131±1 vs. 155±2 IU/L; p<0.01). At 350 μg/L, the inhibition percentage for imipramine 19.2% after 1 h and 20.2% after 2 h. Amitriptyline was a stronger inhibitor: 26% after 30 min at 125 μg/L. At 250 μg/L, the inhibition percentage for amitriptyline was 36.5% after 30 min (100±4 vs. 159±2 IU/L; p<0.01).
Conclusions: The tested tricyclic antidepressants significantly inhibit PON1 activity in a concentration-dependent manner. Amitriptyline had a higher inhibition potency than imipramine.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
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- In vitro effects of three antidepressant drugs on plasma paraoxonase activity
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Articles in the same Issue
- Masthead
- Masthead
- Editorial
- Maintain the goals of Drug Metabolism and Drug Interactions
- Reviews
- Cytochrome P450 2B6: function, genetics, and clinical relevance
- In silico pharmacology for a multidisciplinary drug discovery process
- Original Articles
- In vitro effects of three antidepressant drugs on plasma paraoxonase activity
- Development of a HPLC method for the determination of losartan urinary metabolic ratio to be used for the determination of CYP2C9 hydroxylation phenotypes
- Interaction of methocarbamol and yeast sucrase induces enzyme inhibition
- Evaluation of the effect of statin use on the acenocoumarol and phenprocoumon maintenance dose
- Exploring structurally conservative blocks as universal templates for modeling eukaryotic cytochrome P450s
