Molecules, Vol. 24, Pages 3808: Synthesis of Novel Nicotinic Ligands with Multimodal Action: Targeting Acetylcholine α4β2, Dopamine and Serotonin Transporters

Molecules, Vol. 24, Pages 3808: Synthesis of Novel Nicotinic Ligands with Multimodal Action: Targeting Acetylcholine α4β2, Dopamine and Serotonin Transporters Molecules doi: 10.3390/molecules24203808 Authors: Juan Pablo González-Gutiérrez Hernán Armando Pessoa-Mahana Patricio Ernesto Iturriaga-Vásquez Miguel Iván Reyes-Parada Nicolas Esteban Guerra-Díaz Martin Hodar-Salazar Franco Viscarra Pablo Paillali Gabriel Núñez-Vivanco Marcos Antonio Lorca-Carvajal Jaime Mella-Raipán María Carolina Zúñiga Nicotinic acetylcholine receptors (nAChRs), serotonin transporters (SERT) and dopamine transporters (DAT) represent targets for the development of novel nicotinic derivatives acting as multiligands associated with different health conditions, such as depressive, anxiety and addiction disorders. In the present work, a series of functionalized esters structurally related to acetylcholine and nicotine were synthesized and pharmacologically assayed with respect to these targets. The synthesized compounds were studied in radioligand binding assays at α4β2 nAChR, h-SERT and h-DAT. SERT experiments showed not radioligand [3H]-paroxetine displacement, but rather an increase in the radioligand binding percentage at the central binding site was observed. Compound 20 showed Ki values of 1.008 ± 0.230 μM for h-DAT and 0.031 ± 0.006 μM for α4β2 nAChR...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research