Premium
Pharmacological Evaluation of Halogenated and Non‐halogenated Arylpiperazin‐1‐yl‐ethyl‐benzimidazoles as D 2 and 5‐HT 2A Receptor Ligands
Author(s) -
Tomić Mirko,
Vasković Djurdjica,
Tovilović Gordana,
Andrić Deana,
Penjišević Jelena,
KostićRajačić Sladjana
Publication year - 2011
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200900168
Subject(s) - chemistry , benzimidazole , affinities , halogenation , receptor , bromine , stereochemistry , binding affinities , potency , chlorine , medicinal chemistry , in vitro , biochemistry , organic chemistry
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 p K i binding ratios slightly above or less than 1, while only 4‐chloro‐6‐(2‐{4‐[3‐(trifluoromethyl)phenyl]piperazin‐1‐yl}ethyl)‐1 H ‐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.