Potential antidepressants: pharmacology of 2-(4-methyl piperazin-1-yl)-1,8-naphthyridine-3-carbonitrile in rodent behavioural models

Serotonin type 3 (5-HT3) antagonists, which find an unflinching place in the management of nausea and emesis are presently screened for their neuro-pharmacological potential in various animal models. In the present study, 2-(4-methyl piperazin-1-yl)-1,8-naphthyridine-3-carbonitrile (NA-2) with an optimal log P and pA2 value comparable to that of ondansetron was screened in rodent models of depression. The acute and chronic (14 days) treatment of the synthetic compound exhibited antidepressant-like effects at the lower dose levels in mice forced swim test (FST). A typical and similar dose-immobility profile was observed in both mice FST and tail suspension test (TST). Interaction studies in FST revealed the reversal of mCPP induced immobility, attenuation of antidepressant effects of fluoxetine and desipramine. Chronic NA-2 treatment restored the behavioural deficits in olfactory bulbectomized (OBX) rats as indicated by reduction in hyperactivity in novel open field test. This preliminary study points to a serotonergic mechanism behind the antidepressant-like effects of NA-2 and invigorates further investigation of analogous compounds in various other models of depression.