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• W1963565991 abstract "Evidence suggests that depression is associated with an increase in the high-affinity conformation of the α2-adrenoceptors in human brain. Such enhanced α2-adrenoceptor activity could explain the deficit in central noradrenergic transmission described in the aetiology of depression. Thus, administration of α2-adrenoceptor antagonists augments noradrenaline levels and provides an effective therapeutic approach for the treatment of depressive disorders. In previous studies, we have characterized three new synthesized guanidine and 2-aminoimidazoline aromatic derivatives (8b, 17b and 20b) as α2-adrenoceptor antagonists that are able to increase extracellular concentration of noradrenaline in rat brain. The purpose of the present study was to evaluate the in vivo antidepressant-like properties of these three new α2-adrenoceptor antagonists. For that aim, compounds were tested on the tail suspension test (TST) and forced swim test (FST), two classically widely-used behavioural paradigms for the evaluation of antidepressant-like activity. Compound 8b significantly reduced the immobility time at 10, 20 and 40 mg/kg doses in both TST and FST. Compound 17b reduced the immobility time at 40 mg/kg in both TST and FST. Compound 20b showed a significant decrease in the immobility time at 20 mg/kg in the TST. As drugs of reference, fluoxetine induced a significant antidepressant-like effect in both TST and FST, while mirtazapine induced a significant antidepressant-like effect only in the FST. Additionally, none of the tested compounds increased locomotor activity or displayed anxiolytic-like properties. These results suggest that these new synthesized α2-adrenoceptor antagonists may be useful as potential antidepressant drugs." @default.
• W1963565991 created "2016-06-24" @default.
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• W1963565991 date "2013-02-01" @default.
• W1963565991 modified "2023-10-13" @default.
• W1963565991 title "Antidepressant-like properties of three new α2-adrenoceptor antagonists" @default.
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• W1963565991 doi "https://doi.org/10.1016/j.neuropharm.2012.09.003" @default.
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