title: Synthesis and 5-HT(1A), 5-HT(2A) receptor activity of new beta-tetralonohydantoins.
abstract: A series of new 3-[4-(4-arylpiperazinyl)-butyl]-beta-tetralonohydantoins (8a-13a) were synthesized. The compounds exhibited high affinity for 5-HT(1A) receptors (K(i)=6 to 55 nM) combined with moderate-to-high 5-HT(2A) receptor affinities (K(i)=45 to 213 nM). The results of in vivo studies indicated that of the compounds tested, 3-[4-(4-phenylpiperazinyl)-butyl-beta-tetralonohydantoin (8a) showed features of full (pre- and postsynaptic) 5-HT(1A) receptor agonists, whereas compounds 9a-13a behaved like antagonists of postsynaptic 5-HT(1A) receptors; additionally, compound 13a produced an effect characteristic of presynaptic 5-HT(1A) receptor agonists. Moreover, compounds 8a and 10a-13a exhibited properties of 5-HT(2A) receptor antagonists. Due to the most interesting 5-HT(1A)/5-HT(2A) functional profile compounds 8a and 13a were further tested for their potential psychotropic activity. In fact, compound 8a (but not 13a) showed diazepam-like anxiolytic activity and behaved like a weak antidepressant.
authors.affiliation: Department of Pharmaceutical Chemistry, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Byrtus
authors.forename: Maciej
authors.initials: M
authors.lastname: Pawłowski
authors.forename: Anna
authors.initials: A
authors.lastname: Czopek
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Bojarski
authors.forename: Beata
authors.initials: B
authors.lastname: Duszyńska
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nowak
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Kłodzińska
authors.forename: Ewa
authors.initials: E
authors.lastname: Tatarczyńska
authors.forename: Anna
authors.initials: A
authors.lastname: Wesołowska
authors.forename: Ewa
authors.initials: E
authors.lastname: Chojnacka-Wójcik
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006827:Hydantoins / Q000138:chemical synthesis* / Q000737:chemistry*; D051379:Mice; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D006827:Hydantoins; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A