title: Pharmacological evaluation of halogenated and non-halogenated arylpiperazin-1-yl-ethyl-benzimidazoles as D(2) and 5-HT(2A) receptor ligands.
abstract: Five groups of previously synthesized and initially screened non-substituted and 4-halogenated arylpiperazin-1-yl-ethyl-benzimidazoles were estimated for their in-vitro binding affinities at the rat D(2) , 5-HT(2A) , and α(1) -adrenergic receptors. Among all these compounds, 2-methoxyphenyl and 2-chlorophenyl piperazines demonstrate the highest affinities for the tested receptors. The effects of 4-halogenation of benzimidazoles reveal that substitution with bromine may greatly increase the affinity of the compounds for the studied receptors, while the effect of substitution with chlorine is less remarkable. Most of the tested components show 5-HT(2A)/D(2) pK(i) binding ratios slightly above or less than 1, while only 4-chloro-6-(2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)-1H-benzimidazole expresses an appropriate higher binding ratio (1.14), which was indicated for atypical neuroleptics. This compound exhibits a non-cataleptic action in rats and prevents d-amphetamine-induced hyperlocomotion in mice, which suggest its atypical antipsychotic potency.
authors.affiliation: Department of Biochemistry, Institute for Biological Research, Belgrade, Serbia. mitomic@ibiss.bg.ac.rs
authors.forename: Mirko
authors.initials: M
authors.lastname: Tomić
authors.forename: Djurdjica
authors.initials: D
authors.lastname: Vasković
authors.forename: Gordana
authors.initials: G
authors.lastname: Tovilović
authors.forename: Deana
authors.initials: D
authors.lastname: Andrić
authors.forename: Jelena
authors.initials: J
authors.lastname: Penjišević
authors.forename: Sladjana
authors.initials: S
authors.lastname: Kostić-Rajačić
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001562:Benzimidazoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001665:Binding Sites; D003913:Dextroamphetamine / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D054879:Halogenation; D008024:Ligands; D051379:Mice; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D001562:Benzimidazoles; D018765:Dopamine Uptake Inhibitors; D008024:Ligands; D044402:Receptor, Serotonin, 5-HT2A; D018340:Receptors, Adrenergic, alpha-1; D017448:Receptors, Dopamine D2; D003913:Dextroamphetamine