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 D1 and D2 dopamine and 5-HT1A serotonin receptors using synaptosomal membranes of the bovine caudate nuclei and hippocampi, respectively. Tritiated SCH 23390 (D1 receptor-selective), spiperone (D2 receptor selective) and 8-OH-DPAT (5-HT1A receptor selective) were employed as the radioligands. Only compound 6 expressed a moderate binding affinity at the dopamine D1 receptor, while the remaining ligands were inefficient or weak competitors of [3H]SCH 23390. Compound 12 was an absolutely inactive competitor of all three radioligands. Also, compound 7 was an inefficient displacer of [3H]-8-OH-DPAT. Compound 19 with a Ki value of 3.5 nM was the most potent competitor of [3H]spiperone and compound 13 (Ki = 3.3 nM) was the most efficient in displacing [3H]-8-OH-DPAT from the 5-HT1A 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.
Kostic-Rajacic
S
S
Institute for Chemistry, Technology and Metallurgy, Belgrade, Yugoslavia.
Soskic
V
V
Joksimovic
J
J
D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D002417:Cattle; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D018490:Serotonin Agents / Q000138:chemical synthesis* / Q000494:pharmacology
D001562:Benzimidazoles; D015259:Dopamine Agents; D010879:Piperazines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D018490:Serotonin Agents