title: 4-phenylselenyl-7-chloroquinoline, a novel multitarget compound with anxiolytic activity: Contribution of the glutamatergic system.
abstract: A growing body of evidence demonstrates that quinoline compounds have attracted much attention in the field of drug development. Accordingly, 4-phenylselenyl-7-chloroquinoline (4-PSQ) is a new quinoline derivative containing selenium, which showed a potential antioxidant, antinociceptive and anti-inflammatory effect. The present study was undertaken to evaluate the anxiolytic-like properties of 4-PSQ. Mice were orally pretreated with 4-PSQ (5-50 mg/kg) or vehicle, 30 min prior to the elevated plus-maze (EPM), light-dark (LDT) or open field (OFT) tests. A time-response curve was carried out by administration of 4-PSQ (50 mg/kg) at different times before the EPM test. The involvement of glutamate uptake/release and Na+, K+-ATPase activity in the anxiolytic-like effect was investigated in cerebral cortices. In addition, the effectiveness of acute treatment with 4-PSQ was evaluated in a model of kainate (KA)-induced anxiety-related behavior. Finally, acute toxicity of this compound was investigated. 4-PSQ produced an anxiolytic-like action, both in EPM and LDT. In OFT, 4-PSQ did not affect locomotor and exploratory activities. 4-PSQ anxiolytic-like effect started at 0.5 h and remained significant up to 72 h after administration. Treatment with 4-PSQ reduced [3H] glutamate uptake, but the [3H] glutamate release and Na+, K+-ATPase activity were not altered. KA-induced anxiety-related behavior was protected by 4-PSQ pretreatment. Additionally, 4-PSQ exposure did not alter urea levels, aspartate (AST) and alanine aminotrasferase (ALT) activities in plasma. Parameters of oxidative stress in brain and liver of mice were not modified by 4-PSQ. Taken together these data demonstrated that the anxiolytic-like effect caused by 4-PSQ seems to be mediated by involvement of the glutamatergic system.
authors.affiliation: Programa de Pós-Graduação em Bioquímica e Bioprospecção, Laboratório de Pesquisa em Farmacologia Bioquímica, Grupo de Pesquisa em Neurobiotecnologia - GPN, CCQFA Universidade Federal de Pelotas, UFPel, Pelotas, RS, Brasil.
authors.forename: Angélica S
authors.initials: AS
authors.lastname: Reis
authors.affiliation: Programa de Pós-Graduação em Bioquímica e Bioprospecção, Laboratório de Pesquisa em Farmacologia Bioquímica, Grupo de Pesquisa em Neurobiotecnologia - GPN, CCQFA Universidade Federal de Pelotas, UFPel, Pelotas, RS, Brasil.
authors.forename: Mikaela
authors.initials: M
authors.lastname: Pinz
authors.affiliation: Programa de Pós-Graduação em Química, Laboratório de Síntese Orgânica Limpa - LASOL, CCQFA, Universidade Federal de Pelotas, UFPel, P.O. Box 354, 96010-900, Pelotas, RS, Brasil.
authors.forename: Luis Fernando B
authors.initials: LFB
authors.lastname: Duarte
authors.affiliation: Programa de Pós-Graduação em Química, Laboratório de Síntese Orgânica Limpa - LASOL, CCQFA, Universidade Federal de Pelotas, UFPel, P.O. Box 354, 96010-900, Pelotas, RS, Brasil.
authors.forename: Juliano A
authors.initials: JA
authors.lastname: Roehrs
authors.affiliation: Programa de Pós-Graduação em Química, Laboratório de Síntese Orgânica Limpa - LASOL, CCQFA, Universidade Federal de Pelotas, UFPel, P.O. Box 354, 96010-900, Pelotas, RS, Brasil.
authors.forename: Diego
authors.initials: D
authors.lastname: Alves
authors.affiliation: Programa de Pós-Graduação em Bioquímica e Bioprospecção, Laboratório de Pesquisa em Farmacologia Bioquímica, Grupo de Pesquisa em Neurobiotecnologia - GPN, CCQFA Universidade Federal de Pelotas, UFPel, Pelotas, RS, Brasil. Electronic address: cristiane_luchese@yahoo.com.br.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Luchese
authors.affiliation: Programa de Pós-Graduação em Bioquímica e Bioprospecção, Laboratório de Pesquisa em Farmacologia Bioquímica, Grupo de Pesquisa em Neurobiotecnologia - GPN, CCQFA Universidade Federal de Pelotas, UFPel, Pelotas, RS, Brasil. Electronic address: ethelwilhelm@yahoo.com.br.
authors.forename: Ethel A
authors.initials: EA
authors.lastname: Wilhelm
mesh_terms: D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D018683:Excitatory Amino Acid Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D016566:Organoselenium Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011581:Psychological Tests; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
chemical_list: C000614720:4-phenylselenyl-7-chloroquinoline; D014151:Anti-Anxiety Agents; D018683:Excitatory Amino Acid Agents; D016566:Organoselenium Compounds; D011804:Quinolines; D014316:Tritium; D018698:Glutamic Acid; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Anxiety; Glutamate; Kainate; Mice; Quinoline; Selenium