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Abstract

Does curcumin or pindolol potentiate fluoxetine's antidepressant effect by a pharmacokinetic or pharmacodynamic interaction?

Author(s): H.A.S. Murad1, M. I. Suliaman2, H. Abdallah3, May Abdulsattar2
1Department of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University (KAU), Jeddah-21589, Saudi Arabia 2Department of Pharmacology, Faculty of Medicine, KAU, Jeddah-21589, SA 3Department of Natural Products, Faculty of Pharmacy, KAU, Jeddah-21589, SA

Correspondence Address:
H.A.S. Murad Department of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University (KAU), Jeddah-21589 Saudi Arabia E-mail: [email protected]


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-HT 1A receptors.



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