title: In vitro effects of three antidepressant drugs on plasma paraoxonase activity.
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.
authors.affiliation: Biochemistry and Toxicology Laboratory, University Hospital of Monastir, Monastir, Tunisia. stu_hamm_smh@yahoo.com
authors.forename: Mohamed Hachem
authors.initials: MH
authors.lastname: Saadaoui
authors.forename: Ilhem
authors.initials: I
authors.lastname: Hellara
authors.forename: Fadoua
authors.initials: F
authors.lastname: Neffati
authors.forename: Anouar
authors.initials: A
authors.lastname: Mechri
authors.forename: Wahiba
authors.initials: W
authors.lastname: Douki
authors.forename: Lotfi
authors.initials: L
authors.lastname: Gaha
authors.forename: Mohamed Fadhel
authors.initials: MF
authors.lastname: Najjar
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology*; D043303:Aryldialkylphosphatase / Q000097:blood*; D006801:Humans
chemical_list: D000928:Antidepressive Agents; D043303:Aryldialkylphosphatase