Neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole augment the effects of antidepressants acting via serotonergic system in the forced swimming test in rats.
Treatment-resistant depression has necessitated new therapeutic strategies in augmenting the therapeutic actions of currently existing antidepressant drugs. The aim of this study was to investigate the possibility of synergistic interaction between 1-(2-trifluoromethylphenyl)-imidazole (TRIM), a novel neuronal nitric oxide synthase (nNOS) inhibitor and conventional antidepressants of different classes in the forced swimming test (FST) in rats. TRIM decreased the immobility time at 50 mg/kg doses in the FST in rats. Treatment with a behaviourally subeffective dose of TRIM (20 mg/kg) augmented the behavioural effect of tricyclic antidepressant imipramine, selective serotonin re-uptake inhibitor (SSRI) citalopram and fluoxetine or selective serotonin reuptake enhancer tianeptine but failed to augment the antidepressant effect of reboxetine, a noradrenaline re-uptake inhibitor, in this test. Therefore inhibition of NOS augments the effects of antidepressants acting on serotonergic system in the FST. Neither TRIM (10-50 mg/kg) nor other drug treatments affected the locomotor activity of animals. These findings are in agreement with the view that antidepressant effects or augmentation of these effects in the FST may be explained with inhibition of NOS activity and this may be a new approach in offering greater therapeutic efficacy of antidepressants acting via serotonergic system.
Department of Pharmacology, Faculty of Medicine, Kocaeli University, 41380 Kocaeli, Turkey. gunerulak@yahoo.com
Güner
G
Ulak
Oguz
O
Mutlu
Füruzan Yildiz
FY
Akar
F Ipek
FI
Komsuoğlu
Pelin
P
Tanyeri
B Faruk
BF
Erden
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D015283:Citalopram / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D000077593:Reboxetine; D012701:Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013550:Swimming / Q000523:psychology*; D013841:Thiazepines / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D015283:Citalopram; D004791:Enzyme Inhibitors; D005473:Fluoxetine; D007093:Imidazoles; D009025:Morpholines; D052248:Nitric Oxide Synthase Type I; D000077593:Reboxetine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D013841:Thiazepines; C050504:tianeptine; C098186:1-(2-trifluoromethylphenyl)imidazole