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Synthesis of several substituted phenylpiperazines behaving as mixed D2/5HT(1A) ligands
dc.creator | Dukić, Slađana | |
dc.creator | Kostić Rajačić, Slađana | |
dc.creator | Dragović, D | |
dc.creator | Šoškić, Vukić | |
dc.creator | Joksimović, J | |
dc.date.accessioned | 2019-05-02T10:43:56Z | |
dc.date.available | 2019-05-02T10:43:56Z | |
dc.date.issued | 1997 | |
dc.identifier.issn | 0022-3573 | |
dc.identifier.uri | https://cer.ihtm.bg.ac.rs/handle/123456789/2831 | |
dc.description.abstract | Twenty-two different compounds have been synthesized with the aim of creating new, mixed D2/5HT(1A) ligands. For this purpose l-substituted phenylpiperazines attached by the N-4 nitrogen to dopaminergic pharmacophores of the 2-(5-benzimidazole)ethyl-, 2-(5-benztriazole)ethyl-, 2-[5-(benzimidazole-2thione)]ethyl- and 2-[6-(1,4-dihydroquinoxaline-2,3-dione)]ethyl-type were selected according to known structure affinity requirements of l-arylpiperazines. All the new compounds were evaluated for in-vitro binding affinity at the dopamine (D1 and D2) and 5-HT(1A) receptors. Synaptosomal membranes prepared from fresh bovine caudate nuclei and hippocampi were used as a source of dopamine and 5-hydroxytryptamine receptors, respectively. [3H]SCH 23390 (D1 selective), [3H]spiperone (D2 selective) and 8-OH-[3H]DPAT (5-HT(1A) selective) were employed as the radio-ligands. None of the compounds expressed affinity for binding at D1 dopamine receptors. Compounds 3b and 4b were inactive 8-OH-[3H]DPAT competitors whereas 1b, 2b and 4b were inactive in the [3H] spiperone-binding assay. The other compounds tested showed fair (1c, 1e, 1f, 2c, 2f, 3b, 3c and 4c) to high (1a, 1d, 2a, 1d, 3a, 3d-3f, 4a, and 4d) affinity in the [3H]spiperone-binding assay, the most potent representative being 4-[2-(5-benzimidazole-2-thione)ethyl]1-(2-methoxyphenyl)piperazine, 3a (K(i)=1.7 nM). In the 8-OH-[3H]DPAT-displacement assay compounds 1b, 1d, 1f, 2b, 2f and 3f behaved as moderate competitors and 1a, 1c, 1e, 2a, 2c, 2d, 3a, 3c-3e, 4a, 4c, 4d and 4f as rather strong competitors; 4-[2-(5-benztriazole)ethyl]-1-(2-methoxyphenyl)piperazine, 2a had the highest binding affinity at the 5-HT(1A) receptors (K(i) = 2.6 nM). Because many antipsychotic and anxiolytic agents behave as mixed dopaminergic and serotonergic ligands, the high affinity of several of these new ligands for binding at both D2 and 5-HT(1A) receptors make them promising candidates deserving further pharmacological evaluation as antipsychotic or anxiolytic pharmaceuticals. | en |
dc.publisher | Blackwell Publishing Ltd | |
dc.relation | Ministry of Science and Technology of Serbia | |
dc.rights | restrictedAccess | |
dc.source | Journal of Pharmacy and Pharmacology | |
dc.subject | binding affinity | |
dc.title | Synthesis of several substituted phenylpiperazines behaving as mixed D2/5HT(1A) ligands | en |
dc.type | article | en |
dc.rights.license | ARR | |
dcterms.abstract | Јоксимовић, Ј; Дукић, С; Драговић, Д; Костић-Рајачић, Слађана; Шошкић, В; | |
dc.rights.holder | J. Pharm. Pharmacol. | |
dc.citation.volume | 49 | |
dc.citation.issue | 10 | |
dc.citation.spage | 1036 | |
dc.citation.epage | 1041 | |
dc.identifier.pmid | 9364416 | |
dc.identifier.doi | 10.1111/j.2042-7158.1997.tb06037.x | |
dc.identifier.scopus | 2-s2.0-0030709249 | |
dc.identifier.wos | A1997YD31400018 | |
dc.type.version | publishedVersion |