title: Investigation of mixed D2/5-HT1A activity of N-heteroarylmethyl-N-phenylpiperazines, N-heteroarylethyl-N-phenylpiperazines and N-heteroarylpropyl-N-phenylpiperazines.
abstract: Eight novel N-heteroarylalkyl-N-phenylpiperazines have been synthesized, chemically characterized and evaluated for in vitro binding affinity at the dopamine and serotonin receptors. Synaptosomal membranes of fresh bovine caudate nuclei (D1 and D2), the membranes of COS-7 cells (D4.4) and those prepared from fresh bovine hippocampi (5-HT1A) were used as a source of the corresponding receptor subtypes. [3H]SCH 23390 (D1-selective), [3H]spiperone (D2- and D4.4-selective) and [3H]-8-OH-DPAT (5-HT1A-selective) served as radioligands. None of the compounds expressed the affinity for the binding at the D1 subtype receptor. Compounds 7-9 containing a single methylene group serving as a bridge between heteroaryl- and N-phenylpiperazine part of the molecule were inactive [3H]spiperone and [3H]-8-OH-DPAT competitors. Ligands 15-19 (three methylene groups connecting heteroaryl- and N-phenylpiperazine part of the molecule) acted as moderate competitors of [3H]spiperone binding at the D2 receptor subtype, with the exception of 15 (a thione) which expressed a high binding affinity at the D2 receptor subtype. Compounds 15-19 behaved as moderate displacers of 8-OH-[3H]DPAT. Among all eight novel ligands only compound 15 expressed a moderate binding affinity at the D4.4 receptor subtype.
authors.affiliation: Faculty of Chemistry, University of Belgrade, Yugoslavia.
authors.forename: G
authors.initials: G
authors.lastname: Roglić
authors.forename: S
authors.initials: S
authors.lastname: Dukić-Stefanović
authors.forename: D
authors.initials: D
authors.lastname: Andrić
authors.forename: S
authors.initials: S
authors.lastname: Kostić-Rajacić
authors.forename: V
authors.initials: V
authors.lastname: Soskić
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002417:Cattle; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D011994:Recombinant Proteins / Q000378:metabolism; D018490:Serotonin Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D010879:Piperazines; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D011994:Recombinant Proteins; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin