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dc.creatorDukić, Slađana
dc.creatorKostić Rajačić, Slađana
dc.creatorDragović, D
dc.creatorŠoškić, Vukić
dc.creatorJoksimović, J
dc.date.accessioned2019-05-02T10:43:56Z
dc.date.available2019-05-02T10:43:56Z
dc.date.issued1997
dc.identifier.issn0022-3573
dc.identifier.urihttps://cer.ihtm.bg.ac.rs/handle/123456789/2831
dc.description.abstractTwenty-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.publisherBlackwell Publishing Ltd
dc.relationMinistry of Science and Technology of Serbia
dc.rightsrestrictedAccess
dc.sourceJournal of Pharmacy and Pharmacology
dc.subjectbinding affinity
dc.titleSynthesis of several substituted phenylpiperazines behaving as mixed D2/5HT(1A) ligandsen
dc.typearticleen
dc.rights.licenseARR
dcterms.abstractЈоксимовић, Ј; Дукић, С; Драговић, Д; Костић-Рајачић, Слађана; Шошкић, В;
dc.rights.holderJ. Pharm. Pharmacol.
dc.citation.volume49
dc.citation.issue10
dc.citation.spage1036
dc.citation.epage1041
dc.identifier.pmid9364416
dc.identifier.doi10.1111/j.2042-7158.1997.tb06037.x
dc.identifier.scopus2-s2.0-0030709249
dc.identifier.wosA1997YD31400018
dc.type.versionpublishedVersion


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