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- W2005398959 abstract "The pharmacological profile and antidepressant potential of cyanodothiepin (BTS 56 424) have been compared to those of dothiepin, cianopramine, and imipramine. Rat brain synaptosomes and human platelets were used to measure the effects of drugs on radiolabeled monoamine uptake in vitro. The 2-nitrile substitution converted the actions of dothiepin from nonselective inhibition of 5-hydroxytryptamine (5-HT) and noradrenaline uptake to those of cyanodothiepin, a potent and very selective 5-HT uptake inhibitor (Ki = 4.8 and 597 nM vs. 5-HT and noradrenaline uptake, respectively; rat brain synaptosomes). Nitrile substitution similarly conferred in vitro 5-HT selectivity on cianopramine (Ki = 0.71 and 15 nM vs. 5-HT and noradrenaline) compared to imipramine. The selectivity of cyanodothiepin as a 5-HT reuptake inhibitor was maintained in vivo in a variety of rodent models. Cianopramine was a more potent but less selective 5-HT reuptake inhibitor than cyanodothiepin in these paradigms. In monoamine-depletor based tests for antidepressant activity, cyanodothiepin was weakly active compared to cianopramine and imipramine; cyanodothiepin was active in the Porsolt test for antidepressants. Compared to cianopramine, cyanodothiepin showed weaker affinity for muscarinic cholinergic and 5-HT2 receptors in vitro and in vivo, and for α1-adrenergic, dopamine (D1 and D2) receptors in vitro. Cyanodothiepin was less sedative than cianopramine and was also a weaker enhancer of drug-induced loss of righting reflex in mice. Overall, cyanodothiepin is a potent and selective 5-HT reuptake inhibitor which exhibits antidepressant potential and probably possesses a lower propensity to induce side effects associated with tricyclic antidepressants. © 1993 Wiley-Liss, Inc." @default.
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- W2005398959 title "Pharmacology of cyanodothiepin (BTS 56 424), a selective 5-hydroxytryptamine reuptake inhibitor" @default.
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- W2005398959 doi "https://doi.org/10.1002/ddr.430290311" @default.
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