title: Combination therapy of imipramine and melatonin: additive antidepressant effect in mouse forced swimming test.
abstract: Although there are tools to treat depressive patients, a considerable amount of the cases remains to be untreated. These drug-resistant patients need new drugs or drug combinations to overcome this problem. Thus, the potential synergistic effect of melatonin on a classical drug, imipramine was evaluated in the present study. To test this hypothesis, porsolt swim test, a test predictive of antidepressant-like action, was conducted in mice. Imipramine at doses of 20 and 40 mg/kg caused no alteration and statistically significant reduction in the duration of immobility in forced swim test, respectively. While 5 mg/kg melatonin had no effect, 10 mg/kg melatonin slightly reduced the duration of immobility. When sub-effective doses of imipramine and melatonin (20 and 5 mg/kg, respectively) were co-administered, there was no alteration in responses compared with those of each drug alone. Likewise, the effective dose of melatonin (10 mg/kg) did not cause any increase in responses to 20 mg/kg imipramine. Although combination of imipramine (40 mg/kg) and melatonin (5 mg/kg) did not exert an antidepressant effect above that of imipramine alone, co-administration of the effective doses (10 and 40 mg/kg for melatonin and imipramine, respectively) displayed an additive effect. There were no significant differences between groups in relation with locomotor activity test. The results show that co-administration of imipramine and melatonin exhibits an additive effect and that there seems to be no interaction between the drugs.
authors.affiliation: Department of Pharmacology, School of Medicine, Kahramanmaraş Sütçü Imam University, Kahramanmaraş, 46100, Turkey. yusufergun@ksu.edu.tr
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Ergün
authors.forename: Fatma Ozlem
authors.initials: FO
authors.lastname: Orhan
authors.forename: Mehmet Fatih
authors.initials: MF
authors.lastname: Karaaslan
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology*; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D008550:Melatonin; D007099:Imipramine