Mixed Dopaminergic/Serotonergic Properties of Several 2‐Substituted 4‐[2‐(5‐Benzimidazole)ethyl]‐1‐arylpiperazines

A series of substituted 4‐[2‐(5‐benzimidazole)ethyl]‐arylpiperazines was synthesized by introducing different substituents into position 2 of benzimidazole ring of 4‐[2‐( N,N ‐di‐ n ‐propyl‐amino)ethyl]‐1,2‐diaminobenzenes. They were evaluated for in vitro binding affinity at the D 1 and D 2 dopamine and 5‐HT 1A serotonin receptors using synaptosomal membranes of the bovine caudate nuclei and hippocampi, respectively. Tritiated SCH 23390 (D 1 receptor‐selective), spiperone (D 2 receptor selective) and 8‐OH‐DPAT (5‐HAT 1A receptor selective) were employed as the radioligands. Only compound 6 expressed a moderate binding affinity at the dopamine D 1 receptor, while the remaining ligands were inefficient or weak competitors of [ 3 H]SCH 23390. Compound 12 was an absolutely inactive competitor of all three radioligands. Also, compound 7 was an inefficient displacer of [ 3 H]‐8‐OH‐DPAT. Compound 19 with a K i value of 3.5 nM was the most potent competitor of [ 3 H]spiperone and compound 13 ( K i = 3.3 nM) was the most efficient in displacing [ 3 H]‐8‐OH‐DPAT from the 5‐HAT 1A serotonin receptor. Ligands 5, 6, 8–11 , and 13–20 expressed mixed dopaminergic/serotonergic activity in nanomolar range of concentrations with varying affinity ratios which strongly depended on the properties of the substituents introduced into position 2 of benzimidazole ring of the parent compounds.