Imipramine In Forced Swim Test Research Articles

Ligand-based Pharmacophore Model for Generation of Active Antidepressant- like Agents from Substituted 1,3,5 Triazine Class.

Although the transition of a lead candidate into a drug is currently structured by well-defined milestone, it is still most challenging and offers no guarantee in success to the end. In fact, ligand-based pharmacophore modeling has become a key motive force for retrieving potential leads across several therapeutic areas. An urgent need towards the development of novel antidepressant agents led us to generate a pharmacophore model from an existing 44 compounds dataset. The best model with one hydrophobic, two ring aromatic, and one positive ionization features was chosen on behalf of the correlation coefficient, sensitivity, specificity, yield of actives and accuracy measures using HypoGen module of Discovery Studio. In house library consisting of 10,000 substituted 1,3,5 triazine derivatives were shortlisted to select four insilico hits. All shortlisted compounds were synthesized and characterized by FTIR, 1H-& 13C-NMR spectroscopy and finally tested for antidepressant-like activity using behavioral models on rats viz. Forced Swim Test (FST) and Elevated Plus Maze (EPM). Two shortlisted compounds with optimal fit values showed a significant decrease in the duration of immobility as compared to standard drug Imipramine in FST while time spent in open arm in enhanced in case of EPM.

Enhancement of antidepressant-like activity by joint administration of imipramine and magnesium in the forced swim test: Behavioral and pharmacokinetic studies in mice

The effect of joint administration of imipramine (IMI) and magnesium (Mg) on antidepressant-like activity was studied in mice using forced swim test (FST). Mg doses ineffective per se (5 and 10 mg/kg) given jointly with IMI also at ineffective doses (10 and 15 mg/kg) resulted in a potent reduction in the immobility time. Since these combined treatments did not influence locomotor activity, the antidepressant-like activity was not due to non-specific behavioral activation. Moreover, we estimated the effect of joint administration of magnesium and IMI in FST on serum and brain magnesium, IMI and its active metabolite desipramine (DMI) concentrations in mice. Swim stress (mice subjected to FST) increased the magnesium concentration in serum and decreased it in the brain compared to naive animals. Moreover administration of IMI increased (normalized) magnesium brain concentration, without influence on the serum level. Joint administration of IMI and magnesium did not influence magnesium (compared with FST) or IMI and DMI (compared with IMI treatment alone) concentrations in both examined tissues. The present data demonstrated an enhancement of the antidepressant-like effect by joint administration of IMI and magnesium in the FST, and further indicate the particular role of magnesium in the antidepressant action. Since there was no increase in IMI, DMI or magnesium concentration after joint administration of magnesium and IMI, the data suggest that pharmacodynamic rather than pharmacokinetic interaction between magnesium and IMI is accountable for behavioral effect in the FST.