Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice
Depression, anxiety, and schizophrenia may coexist in psychiatric patients. Moreover, these disorders are very often associated with cognitive impairments. However, pharmacotherapy of these conditions remains challenging due to limited drug effectiveness or numerous side effects. Therefore, there is...
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MDPI AG
2023-01-01
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| Online Access: | https://www.mdpi.com/1424-8247/16/2/175 |
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| author | Elżbieta Żmudzka Klaudia Lustyk Monika Głuch-Lutwin Małgorzata Wolak Jolanta Jaśkowska Marcin Kołaczkowski Jacek Sapa Karolina Pytka |
| author_facet | Elżbieta Żmudzka Klaudia Lustyk Monika Głuch-Lutwin Małgorzata Wolak Jolanta Jaśkowska Marcin Kołaczkowski Jacek Sapa Karolina Pytka |
| author_sort | Elżbieta Żmudzka |
| collection | DOAJ |
| description | Depression, anxiety, and schizophrenia may coexist in psychiatric patients. Moreover, these disorders are very often associated with cognitive impairments. However, pharmacotherapy of these conditions remains challenging due to limited drug effectiveness or numerous side effects. Therefore, there is an urgent need to develop novel multimodal compounds that can be used to treat depression, anxiety, and schizophrenia, as well as memory deficits. Thus, this study aimed to evaluate the potential antidepressant-like, anxiolytic-like, antipsychotic-like effects, and anti-amnesic properties, of the novel arylpiperazine derivative of salicylamide, JJGW07, with an affinity towards serotonin 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, and 5-HT<sub>7</sub> and dopamine D<sub>2</sub> receptors. Firstly, we investigated the compound’s affinity for 5-HT<sub>6</sub> receptors and its functional activity by using in vitro assays. JJGW07 did not bind to 5-HT<sub>6</sub> receptors and showed antagonistic properties for 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, 5-HT<sub>7</sub>, and D<sub>2</sub> receptors. Based on the receptor profile, we performed behavioral studies in mice to evaluate the antidepressant-like, anxiolytic-like, and antipsychotic-like activity of the tested compound using forced swim and tail suspension tests; four-plate, marble-burying, and elevated plus maze tests; and MK-801- and amphetamine-induced hyperlocomotion tests, respectively. JJGW07 revealed antidepressant-like properties in the tail suspension test, anxiolytic-like effects in the four-plate and marble-burying tests, and antipsychotic-like activity in the MK-801-induced hyperlocomotion test. Importantly, the tested compound did not induce catalepsy and motor impairments or influence locomotor activity in rodents. Finally, to assess the potential procognitive and anti-amnesic properties of JJGW07, we used passive avoidance and object recognition tests in mice. JJGW07 demonstrated positive effects on long-term emotional memory and also ameliorated MK-801-induced emotional memory impairments in mice, but showed no procognitive properties in the case of recognition memory. Our results encourage the search for new compounds among salicylamide derivatives, which could be model structures with multitarget mechanisms of action that could be used in psychiatric disorder therapy. |
| first_indexed | 2024-03-11T08:17:32Z |
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| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T08:17:32Z |
| publishDate | 2023-01-01 |
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| spelling | doaj.art-01f15a7cad704a1ca5769770a4dc6d632023-11-16T22:36:03ZengMDPI AGPharmaceuticals1424-82472023-01-0116217510.3390/ph16020175Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in MiceElżbieta Żmudzka0Klaudia Lustyk1Monika Głuch-Lutwin2Małgorzata Wolak3Jolanta Jaśkowska4Marcin Kołaczkowski5Jacek Sapa6Karolina Pytka7Department of Social Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, PolandDepartment of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, PolandDepartment of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, PolandDepartment of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, PolandDepartment of Organic Chemistry and Technology, Faculty of Chemical and Engineering and Technology, Cracow University of Technology, Warszawska 24, 31-155 Krakow, PolandDepartment of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, PolandDepartment of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, PolandDepartment of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, PolandDepression, anxiety, and schizophrenia may coexist in psychiatric patients. Moreover, these disorders are very often associated with cognitive impairments. However, pharmacotherapy of these conditions remains challenging due to limited drug effectiveness or numerous side effects. Therefore, there is an urgent need to develop novel multimodal compounds that can be used to treat depression, anxiety, and schizophrenia, as well as memory deficits. Thus, this study aimed to evaluate the potential antidepressant-like, anxiolytic-like, antipsychotic-like effects, and anti-amnesic properties, of the novel arylpiperazine derivative of salicylamide, JJGW07, with an affinity towards serotonin 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, and 5-HT<sub>7</sub> and dopamine D<sub>2</sub> receptors. Firstly, we investigated the compound’s affinity for 5-HT<sub>6</sub> receptors and its functional activity by using in vitro assays. JJGW07 did not bind to 5-HT<sub>6</sub> receptors and showed antagonistic properties for 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, 5-HT<sub>7</sub>, and D<sub>2</sub> receptors. Based on the receptor profile, we performed behavioral studies in mice to evaluate the antidepressant-like, anxiolytic-like, and antipsychotic-like activity of the tested compound using forced swim and tail suspension tests; four-plate, marble-burying, and elevated plus maze tests; and MK-801- and amphetamine-induced hyperlocomotion tests, respectively. JJGW07 revealed antidepressant-like properties in the tail suspension test, anxiolytic-like effects in the four-plate and marble-burying tests, and antipsychotic-like activity in the MK-801-induced hyperlocomotion test. Importantly, the tested compound did not induce catalepsy and motor impairments or influence locomotor activity in rodents. Finally, to assess the potential procognitive and anti-amnesic properties of JJGW07, we used passive avoidance and object recognition tests in mice. JJGW07 demonstrated positive effects on long-term emotional memory and also ameliorated MK-801-induced emotional memory impairments in mice, but showed no procognitive properties in the case of recognition memory. Our results encourage the search for new compounds among salicylamide derivatives, which could be model structures with multitarget mechanisms of action that could be used in psychiatric disorder therapy.https://www.mdpi.com/1424-8247/16/2/175antidepressant-like activityanxiolytic-like actionantipsychotic-like propertiesanti-amnesic effectmemory-enhancingserotonin receptor antagonist |
| spellingShingle | Elżbieta Żmudzka Klaudia Lustyk Monika Głuch-Lutwin Małgorzata Wolak Jolanta Jaśkowska Marcin Kołaczkowski Jacek Sapa Karolina Pytka Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice Pharmaceuticals antidepressant-like activity anxiolytic-like action antipsychotic-like properties anti-amnesic effect memory-enhancing serotonin receptor antagonist |
| title | Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice |
| title_full | Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice |
| title_fullStr | Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice |
| title_full_unstemmed | Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice |
| title_short | Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice |
| title_sort | novel multimodal salicylamide derivative with antidepressant like anxiolytic like antipsychotic like and anti amnesic activity in mice |
| topic | antidepressant-like activity anxiolytic-like action antipsychotic-like properties anti-amnesic effect memory-enhancing serotonin receptor antagonist |
| url | https://www.mdpi.com/1424-8247/16/2/175 |
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