Antipsychotic- and Anxiolytic-like Properties of a Multimodal Compound JJGW08 in Rodents
Schizophrenia is a chronic mental illness, which remains difficult to treat. A high resistance to the available therapies, their insufficient efficacy, and numerous side effects are the reasons why there is an urgent need to develop new antipsychotics. This study aimed to assess the antipsychotic-li...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/15929 |
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| author | Elżbieta Żmudzka Klaudia Lustyk Monika Głuch-Lutwin Barbara Mordyl Alicja Zakrzewska-Sito Paweł Mierzejewski Jolanta Jaśkowska Marcin Kołaczkowski Jacek Sapa Karolina Pytka |
| author_facet | Elżbieta Żmudzka Klaudia Lustyk Monika Głuch-Lutwin Barbara Mordyl Alicja Zakrzewska-Sito Paweł Mierzejewski Jolanta Jaśkowska Marcin Kołaczkowski Jacek Sapa Karolina Pytka |
| author_sort | Elżbieta Żmudzka |
| collection | DOAJ |
| description | Schizophrenia is a chronic mental illness, which remains difficult to treat. A high resistance to the available therapies, their insufficient efficacy, and numerous side effects are the reasons why there is an urgent need to develop new antipsychotics. This study aimed to assess the antipsychotic-like effects of JJGW08, a novel arylpiperazine alkyl derivative of salicylamide, in rodents. First, considering the JJGW08 receptor profile, we investigated the compound’s intrinsic activity towards dopamine D<sub>2</sub> and serotonin 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, and 5-HT<sub>7</sub> receptors using functional assays. Next, we assessed the effect of JJGW08 on MK-801- and amphetamine-induced hyperlocomotion, its risk of inducing catalepsy and impairing motor coordination, as well as the anxiolytic-like effects in the four-plate and marble burying tests in mice. Finally, we investigated the antipsychotic-like properties of JJGW08 in rats using MK-801-induced hyperlocomotion and prepulse inhibition tests. We found that JJGW08 showed antagonistic properties at dopamine D<sub>2</sub> and serotonin 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, and 5-HT<sub>7</sub> receptors. However, the effect on the 5-HT<sub>2A</sub> and 5-HT<sub>7</sub> receptors was very weak. Moreover, the tested compound showed an antipsychotic-like effect in MK-801- and amphetamine-induced hyperlocomotion but not in a prepulse inhibition test in rats. Notably, JJGW08 demonstrated anxiolytic-like properties in both behavioral tests. Importantly, the compound did not induce catalepsy or motor coordination impairment in mice at antipsychotic-like doses. Our study suggests it is worth searching for new potential antipsychotics among arylpiperazine alkyl derivatives of salicylamide. |
| first_indexed | 2024-03-09T09:45:26Z |
| format | Article |
| id | doaj.art-0b286050b9a844048be66d18514d16f1 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T09:45:26Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0b286050b9a844048be66d18514d16f12023-12-02T00:36:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241592910.3390/ijms232415929Antipsychotic- and Anxiolytic-like Properties of a Multimodal Compound JJGW08 in RodentsElżbieta Żmudzka0Klaudia Lustyk1Monika Głuch-Lutwin2Barbara Mordyl3Alicja Zakrzewska-Sito4Paweł Mierzejewski5Jolanta Jaśkowska6Marcin Kołaczkowski7Jacek Sapa8Karolina Pytka9Department 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 Pharmacology, Institute of Psychiatry and Neurology, Sobieskiego 9, 02-957 Warszawa, PolandDepartment of Pharmacology, Institute of Psychiatry and Neurology, Sobieskiego 9, 02-957 Warszawa, 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, PolandSchizophrenia is a chronic mental illness, which remains difficult to treat. A high resistance to the available therapies, their insufficient efficacy, and numerous side effects are the reasons why there is an urgent need to develop new antipsychotics. This study aimed to assess the antipsychotic-like effects of JJGW08, a novel arylpiperazine alkyl derivative of salicylamide, in rodents. First, considering the JJGW08 receptor profile, we investigated the compound’s intrinsic activity towards dopamine D<sub>2</sub> and serotonin 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, and 5-HT<sub>7</sub> receptors using functional assays. Next, we assessed the effect of JJGW08 on MK-801- and amphetamine-induced hyperlocomotion, its risk of inducing catalepsy and impairing motor coordination, as well as the anxiolytic-like effects in the four-plate and marble burying tests in mice. Finally, we investigated the antipsychotic-like properties of JJGW08 in rats using MK-801-induced hyperlocomotion and prepulse inhibition tests. We found that JJGW08 showed antagonistic properties at dopamine D<sub>2</sub> and serotonin 5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, and 5-HT<sub>7</sub> receptors. However, the effect on the 5-HT<sub>2A</sub> and 5-HT<sub>7</sub> receptors was very weak. Moreover, the tested compound showed an antipsychotic-like effect in MK-801- and amphetamine-induced hyperlocomotion but not in a prepulse inhibition test in rats. Notably, JJGW08 demonstrated anxiolytic-like properties in both behavioral tests. Importantly, the compound did not induce catalepsy or motor coordination impairment in mice at antipsychotic-like doses. Our study suggests it is worth searching for new potential antipsychotics among arylpiperazine alkyl derivatives of salicylamide.https://www.mdpi.com/1422-0067/23/24/15929antipsychotic-like activityanxiolytic-like effectD<sub>2</sub> receptor antagonist5-HT<sub>1A</sub> receptor antagonistarylpiperazine derivative of salicylamide |
| spellingShingle | Elżbieta Żmudzka Klaudia Lustyk Monika Głuch-Lutwin Barbara Mordyl Alicja Zakrzewska-Sito Paweł Mierzejewski Jolanta Jaśkowska Marcin Kołaczkowski Jacek Sapa Karolina Pytka Antipsychotic- and Anxiolytic-like Properties of a Multimodal Compound JJGW08 in Rodents International Journal of Molecular Sciences antipsychotic-like activity anxiolytic-like effect D<sub>2</sub> receptor antagonist 5-HT<sub>1A</sub> receptor antagonist arylpiperazine derivative of salicylamide |
| title | Antipsychotic- and Anxiolytic-like Properties of a Multimodal Compound JJGW08 in Rodents |
| title_full | Antipsychotic- and Anxiolytic-like Properties of a Multimodal Compound JJGW08 in Rodents |
| title_fullStr | Antipsychotic- and Anxiolytic-like Properties of a Multimodal Compound JJGW08 in Rodents |
| title_full_unstemmed | Antipsychotic- and Anxiolytic-like Properties of a Multimodal Compound JJGW08 in Rodents |
| title_short | Antipsychotic- and Anxiolytic-like Properties of a Multimodal Compound JJGW08 in Rodents |
| title_sort | antipsychotic and anxiolytic like properties of a multimodal compound jjgw08 in rodents |
| topic | antipsychotic-like activity anxiolytic-like effect D<sub>2</sub> receptor antagonist 5-HT<sub>1A</sub> receptor antagonist arylpiperazine derivative of salicylamide |
| url | https://www.mdpi.com/1422-0067/23/24/15929 |
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