Investigation of mixed D(2)/5-HT(1A) activity of N-heteroarylmethyl-N-phenylpiperazines, N-heteroarylethyl-N-phenylpiperazines and N-heteroarylpropyl-N-phenylpiperazines
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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 (D(1) and D(2)), the membranes of COS-7 cells (D(4.4)) and those prepared from fresh bovine hippocampi (5-HT(1A)) were used as a source of the corresponding receptor subtypes. [(3)H]SCH 23390 (D(1)-selective), [(3)H]spiperone (D(2)- and D(4.4)- selective) and [(3)H]-8-OH-DPAT (5-HT(1A)-selective) served as radioligands. None of the compounds expressed the affinity for the binding at the D(1) 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 [(3)H]spiperone and [(3)H]-8-OH-DPAT competitors. Ligands 15-19 (three methylene groups connecting heteroaryl- and N-phenylpiperazine part of the molecule) acted as moderate competitors of [(3)H]spiperon...e binding at the D(2) receptor subtype, with the exception of 15 (a thione) which expressed a high binding affinity at the D(2) receptor subtype. Compounds 15-19 behaved as moderate displacers of 8-OH-[(3)H]DPAT. Among all eight novel ligands only compound 15 expressed a moderate binding affinity at the D(4.4) receptor subtype.
Source:Pharmazie, 2001, 56, 10, 803-807
- Govi-Verlag Pharmazeutischer Verlag Gmbh, Eschborn