Antidepressant effect and toxicity of a new morpholino betalactam compound in male mice

Introduction: In this study the antidepressant effect of a new morpholino betalactam composition, 1-(3- morpholinopropyl)-4-(naphthalene-2-yl)-3-phenoxyazetidin-2-one (EB9) administered at three doses, was investigated in an animal model of depression. The CNS stimulant, muscle coordination and toxic effects of this compound were also tested. Methods: Morpholino betalactam at 10, 15 and 20 mg/kg, imipramine at 5, 10 and 20 mg/kg as a positive control and two solvents, distilled water and DMSO as negative controls were administered to white male mice. After a forced swimming pretest, the mice received two i.p. injections, the first one immediately after, and the second one five hours after the pretest. The duration of immobility and climbing behaviors, at 1 and 23.5 hours after the first injection were recorded as acute and subacute effects, respectively. For the evaluation of muscle coordination, rotarod test was used. Total activity test was done to test the CNS stimulant effect. Toxicity of the compound at the doses of 300-400 mg/kg was also studied and its LD50 was calculated. Results: The new morpholino betalactam compound significantly reduced the immobility time and increased the climbing time in the forced swimming test, without showing any significant effect on the total activity and rotarod test results. At the dose of 400 mg/kg, the compound caused liver damage and its LD50 was estimated to be 325 mg/kg. Conclusion: Morpholino betalactam may have antidepressant effect in human at doses which are not toxic.