title: Does Curcumin or Pindolol Potentiate Fluoxetine's Antidepressant Effect by a Pharmacokinetic or Pharmacodynamic Interaction?
abstract: This study was designed to study potentiation of fluoxetine's antidepressant effect by curcumin or pindolol. Twenty eight groups of mice (n=8) were used in three sets of experiments. In the first set, 9 groups were subjected to the forced swimming test after being treated intraperitoneally with three vehicles, fluoxetine (5 and 20 mg/kg), curcumin (20 mg/kg), pindolol (32 mg/kg), curcumin+fluoxetine (5 mg/kg) and pindolol+fluoxetine (5 mg/kg). One hour after the test, serum and brain fluoxetine and norfluoxetine levels were measured in mice receiving fluoxetine (5 and 20 mg/kg), curcumin+fluoxetine (5 mg/kg) and pindolol+fluoxetine (5 mg/kg). In the second set, the test was done after pretreatment with p-chlorophenylalanine. In the third set, the locomotor activity was measured. The immobility duration was significantly decreased in fluoxetine (20 mg/kg), curcumin (20 mg/kg), curcumin+fluoxetine (5 mg/kg) and pindolol+fluoxetine (5 mg/kg) groups. These decreases were reversed with p-chlorophenylalanine. Fluoxetine and norfluoxetine levels were significantly higher in fluoxetine (20 mg/kg) group with no differences in fluoxetine (5 mg/kg), curcumin+fluoxetine (5 mg/kg) and pindolol+fluoxetine (5 mg/kg) groups. Moreover, drugs failed to alter the locomotor activity indicating absence of central stimulation. In conclusion, curcumin, more than pindolol enhanced the antidepressant effect of a subeffective dose of fluoxetine in mice without increasing its serum or brain levels excluding any pharmacokinetic interaction. Reversal of this potentiation with p-chlorophenylalanine suggests a pharmacodynamic interaction through involvement of presynaptic 5-HT1A receptors.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University (KAU), Jeddah-21589, Saudi Arabia (SA) and Faculty of Medicine, Ain Shams University, Cairo-11541, Egypt.
authors.forename: H A S
authors.initials: HA
authors.lastname: Murad
authors.affiliation: Department of Pharmacology, Faculty of Medicine, KAU, Jeddah-21589, SA.
authors.forename: M I
authors.initials: MI
authors.lastname: Suliaman
authors.affiliation: Department of Natural Products, Faculty of Pharmacy, KAU, Jeddah-21589, SA and Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo-11541, Egypt.
authors.forename: H
authors.initials: H
authors.lastname: Abdallah
authors.affiliation: Department of Pharmacology, Faculty of Medicine, KAU, Jeddah-21589, SA.
authors.forename: May
authors.initials: M
authors.lastname: Abdulsattar
keywords: Curcumin; fluoxetine; forced swimming test; pharmacodynamic; pharmacokinetic; pindolol