Introduction of a methyl group in α‐ or β‐position of 1‐heteroarylethyl‐4‐phenyl‐piperazines affects their dopaminergic/serotonergic properties

摘要: 1-(2-Heteroarylalkyl)-4-phenylpiperazines containing methyl group in either the alpha- or beta-position of side alkyl chain were synthesized as racemic mixtures. They evaluated for vitro binding affinity at D1 and D2 dopamine 5-HT1A serotonin receptors using synaptosomal membranes bovine caudate nucleus hippocampus, respectively, a source corresponding receptors. Tritiated SCH 23390 (D1 receptor-selective), spiperone (D2 8-OH-DPAT (5-HT1A receptor-selective) employed radioligands. None new compounds expressed significant receptor. Introduction into parent molecules increased receptor (10b-13b), decreased with exception imidazole (11b) which was rather efficient displacer 8-OH-DPAT. Most potent newly [3H]spiperone assay (+/-)6-[1-methyl-2- (4-phenylpiperazin-1-yl)-ethyl]-1,4-dihydroquinoxaline-2,3-dione (10b), Kd = 6.0 nM (+/-)5-[1-methyl-2-(4-phenylpiperazin-1-yl)-ethyl]-1,3-dihydrobenzoimidazol- 2-thione (13b), 5.3 nM. However, alpha-position (10a-13a) receptor, while remained same range concentrations that closely related achiral (14-17) run assays references.