In vitro effects of three antidepressant drugs on plasma paraoxonase activity
Identifieur interne : 000421 ( Main/Exploration ); précédent : 000420; suivant : 000422In vitro effects of three antidepressant drugs on plasma paraoxonase activity
Auteurs : Mohamed Hachem Saadaoui [Tunisie] ; Ilhem Hellara [Tunisie] ; Fadoua Neffati [Tunisie] ; Anouar Mechri [Tunisie] ; Wahiba Douki ; Lotfi Gaha [Tunisie] ; Mohamed Fadhel Najjar [Tunisie]Source :
- Drug Metabolism and Drug Interactions [ 0792-5077 ] ; 2012-12-01.
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.
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DOI: 10.1515/dmdi-2012-0015
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ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Tunisie</li></country></list><tree><noCountry><name sortKey="Douki, Wahiba" sort="Douki, Wahiba" uniqKey="Douki W" first="Wahiba" last="Douki">Wahiba Douki</name></noCountry><country name="Tunisie"><noRegion><name sortKey="Saadaoui, Mohamed Hachem" sort="Saadaoui, Mohamed Hachem" uniqKey="Saadaoui M" first="Mohamed Hachem" last="Saadaoui">Mohamed Hachem Saadaoui</name></noRegion><name sortKey="Gaha, Lotfi" sort="Gaha, Lotfi" uniqKey="Gaha L" first="Lotfi" last="Gaha">Lotfi Gaha</name><name sortKey="Hellara, Ilhem" sort="Hellara, Ilhem" uniqKey="Hellara I" first="Ilhem" last="Hellara">Ilhem Hellara</name><name sortKey="Mechri, Anouar" sort="Mechri, Anouar" uniqKey="Mechri A" first="Anouar" last="Mechri">Anouar Mechri</name><name sortKey="Najjar, Mohamed Fadhel" sort="Najjar, Mohamed Fadhel" uniqKey="Najjar M" first="Mohamed Fadhel" last="Najjar">Mohamed Fadhel Najjar</name><name sortKey="Neffati, Fadoua" sort="Neffati, Fadoua" uniqKey="Neffati F" first="Fadoua" last="Neffati">Fadoua Neffati</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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