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Although a variety of single drugs are used in the treatment of anxiety, it is important to search for new therapeutics with faster onset of action, fewer side effects, and higher efficacy. In this work, we studied the possible anxiolytic action mechanism of two new arylpiperazine derivatives: compounds\n                    <jats:bold>4p<\/jats:bold>\n                    <jats:italic>N<\/jats:italic>\n                    \u2010(3\u2010(4\u2010(piperonyl)piperazin\u20101\u2010yl)propyl)isonicotinamide and\n                    <jats:bold>3o<\/jats:bold>\n                    <jats:italic>N<\/jats:italic>\n                    \u2010(2\u2010(4\u2010(pyrimidin\u20102\u2010yl)piperazin\u20101\u2010yl)ethyl)picolinamide, focusing on their effects on the GABAergic and 5\u2010HT systems. The elevated plus\u2010maze test (EPM) was used for measuring anxiety. Additionally, in order to elucidate whether the new compounds have impact on the central redox balance, we conducted biochemical studies. In doing so, the relative activity of the enzymes responsible for glutathione metabolism \u2013 glutathione peroxidase and reductase (GPx and GR) \u2013 was measured. The results of the presented studies confirmed the anxiolytic effects of the new compounds\n                    <jats:bold>4p<\/jats:bold>\n                    (60 mg\/kg) and\n                    <jats:bold>3o<\/jats:bold>\n                    (7.5 mg\/kg), and suggested in the mechanism of their action, direct 5\u2010HT\n                    <jats:sub>1A<\/jats:sub>\n                    receptors\u2019 participation and indirect involvement of the GABAergic system. Furthermore, the compounds exerted significant agonistic effect with buspirone (BUS, the 5\u2010HT\n                    <jats:sub>1A<\/jats:sub>\n                    partial agonist, 1 mg\/kg i.p.) and diazepam (DZ, the classic benzodiazepine anxiolytic, 0.25 mg\/kg s.c.), while WAY 100635 (\n                    <jats:italic>N<\/jats:italic>\n                    \u2010{2\u2010[4\u2010(2\u2010methoxyphenyl)\u20101\u2010piperazinyl] ethyl}\u2010\n                    <jats:italic>N<\/jats:italic>\n                    \u2010(2\u2010pyridyl) cyclohexanecarboxamide, a selective 5\u2010HT\n                    <jats:sub>1A<\/jats:sub>\n                    antagonist, 0.1 mg\/kg s.c.), but not flumazenil (a GABA\n                    <jats:sub>A<\/jats:sub>\n                    \u2010BDZ receptor complex antagonist, 10 mg\/kg i.p.) was able to reverse their anxiolytic effects in EPM. A concomitant decrease in GPx by the compound\n                    <jats:bold>4p<\/jats:bold>\n                    (and to a lesser degree, by compound\n                    <jats:bold>3o<\/jats:bold>\n                    ) further seemed to confirm their anxiolytic and antioxidant activity.\n                  <\/jats:p>","DOI":"10.1111\/fcp.12443","type":"journal-article","created":{"date-parts":[[2018,12,2]],"date-time":"2018-12-02T06:34:11Z","timestamp":1543732451000},"page":"254-266","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Anxiolytic\u2010like effects of the new arylpiperazine derivatives containing isonicotinic and picolinic nuclei: behavioral and biochemical studies"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2648-6075","authenticated-orcid":false,"given":"Ewa","family":"K\u0119dzierska","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics Faculty of Pharmacy with Division of Medical Analytics Medical University of Lublin Chod\u017aki 4a 20\u2010093 Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferdinando","family":"Fiorino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Naples Federico II Via D. Montesano 49 80131 Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Gibu\u0142a","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics Faculty of Pharmacy with Division of Medical Analytics Medical University of Lublin Chod\u017aki 4a 20\u2010093 Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Corvino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Naples Federico II Via D. Montesano 49 80131 Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavia","family":"Giordano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Naples Federico II Via D. Montesano 49 80131 Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariola","family":"Herbet","sequence":"additional","affiliation":[{"name":"Department of Toxicology Faculty of Pharmacy with Division of Medical Analytics Medical University of Lublin Chod\u017aki 8 20\u2010093 Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaros\u0142aw","family":"Dudka","sequence":"additional","affiliation":[{"name":"Department of Toxicology Faculty of Pharmacy with Division of Medical Analytics Medical University of Lublin Chod\u017aki 8 20\u2010093 Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Poleszak","sequence":"additional","affiliation":[{"name":"Department of Applied Pharmacy Faculty of Pharmacy with Division of Medical Analytics Medical University of Lublin Chod\u017aki 1 20\u2010093 Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Wla\u017a","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology Faculty of Biology and Biotechnology Maria Curie\u2010Sk\u0142odowska University Akademicka 19 20\u2010033 Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4178-1515","authenticated-orcid":false,"given":"Jolanta H.","family":"Kotli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacodynamics Faculty of Pharmacy with Division of Medical Analytics Medical University of Lublin Chod\u017aki 4a 20\u2010093 Lublin Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,1,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2011.09.023"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.31887\/DCNS.2015.17.3\/bbandelow"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12186"},{"key":"e_1_2_6_5_1","first-page":"87","article-title":"Miejsce l\u0119ku w obrazie psychopatologicznym depresji","volume":"8","author":"Zi\u0119ba A.","year":"2003","journal-title":"L\u0119k i Depresja."},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.2009.01382.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1192\/S0007125000298371"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0327(95)00002-5"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200868120-00002"},{"issue":"6","key":"e_1_2_6_10_1","first-page":"22","article-title":"Anxiety symptom relief in depression treatment outcomes","volume":"56","author":"Keller M.B.","year":"1995","journal-title":"J. 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