Synergistic effect of [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one] and antidepressant drugs in the mouse forced swimming test: possible involvement of serotonergic pathway.
To augment the effects of classical antidepressant drugs by combination therapies in drug-resistant patients has been an emerging treatment strategy. In the present study, the potential synergistic effect of [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one] (ODQ) and antidepressant drugs in the forced swimming test was evaluated. While 5mg/kg intraperitoneal administration of imipramine, fluoxetine or desipramine caused no effect in the duration of immobility in the forced swimming test (sub-effective doses), higher doses (20, 10 and 10mg/kg, respectively) reduced the immobility period (effective doses). When sub-effective doses of ODQ (15mg/kg) and imipramine (5mg/kg) were applied, there was a significant reduction in the immobility time compared with those of each drug alone. Similarly the reduction seen with the effective dose of imipramine (20mg/kg) was also augmented by the co-administration of ODQ (15mg/kg). By its sub-effective dose, ODQ exerted statistically significant augmentations in the responses to either sub-effective (5mg/kg) or effective dose (10mg/kg) of fluoxetine. By contrast, desipramine was not influenced by the co-administration of ODQ (15mg/kg). None of the drugs used in the present study had any effects on the locomotor activity test over the dose range applied. The results show that co-administration of imipramine/fluoxetine and ODQ exhibits a supra-additive effect and that serotonergic rather than noradrenergic pathway may be involved in the synergistic effect of ODQ.
Ergün
Yusuf
Y
Kahramanmaraş Sütçü Imam University, School of Medicine, Department of Pharmacology, Kahramanmaraş, 46100, Turkey. yusufergun@ksu.edu.tr <yusufergun@ksu.edu.tr>
Orhan
Ozlem Fatma
OF
Ozer
Ufuk Güney
UG
Gişi
Gökçe
G
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D004357:Drug Synergism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010069:Oxadiazoles / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism*; D013550:Swimming; D013997:Time Factors
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000928:Antidepressive Agents; D010069:Oxadiazoles; D011810:Quinoxalines; D012701:Serotonin