Pharmacological Evaluation of Halogenated and Non-halogenated Arylpiperazin-1-yl-ethyl-benzimidazoles as D2 and 5-HT2A Receptor Ligands

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 D2, 5‐HT2A, and α1‐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‐HT2A/D2 pKi 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. An actual trend in neuropharmacology is a quest for new atypical antipsychotics that are more efficacious and have fewer side effects. Five groups of arylpiperazines were pharmacologically screened and one compound was initially evaluated by behavioral tests for its atypical antipsychotic potency.