The Antiarrhythmic Activity of Novel Pyrrolidin-2-one Derivative S-75 in Adrenaline-Induced Arrhythmia
Arrhythmia is a quivering or irregular heartbeat that can often lead to blood clots, stroke, heart failure, and other heart-related complications. The limited efficacy and safety of antiarrhythmic drugs require the design of new compounds. Previous research indicated that pyrrolidin-2-one derivative...
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2021
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oai:doaj.org-article:919015ed90c64d18ab47d372690bf4052021-11-25T18:39:02ZThe Antiarrhythmic Activity of Novel Pyrrolidin-2-one Derivative S-75 in Adrenaline-Induced Arrhythmia10.3390/ph141110651424-8247https://doaj.org/article/919015ed90c64d18ab47d372690bf4052021-10-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1065https://doaj.org/toc/1424-8247Arrhythmia is a quivering or irregular heartbeat that can often lead to blood clots, stroke, heart failure, and other heart-related complications. The limited efficacy and safety of antiarrhythmic drugs require the design of new compounds. Previous research indicated that pyrrolidin-2-one derivatives possess an affinity for α<sub>1</sub>-adrenergic receptors. The blockade of α<sub>1</sub>-adrenoceptor may play a role in restoring normal sinus rhythm; therefore, we aimed to verify the antiarrhythmic activity of novel pyrrolidin-2-one derivative S-75. In this study, we assessed the influence on sodium, calcium, potassium channels, and β<sub>1</sub>-adrenergic receptors to investigate the mechanism of action of S-75. Lack of affinity for β<sub>1</sub>-adrenoceptors and weak effects on ion channels decreased the role of these adrenoceptors and channels in the pharmacological activity of S-75. Next, we evaluated the influence of S-75 on normal ECG in rats and isolated rat hearts, and the tested derivative did not prolong the QT<sub>c</sub> interval, which may confirm the lack of the proarrhythmic potential. We tested antiarrhythmic activity in adrenaline-, aconitine- and calcium chloride-induced arrhythmia models in rats. The studied compound showed prophylactic antiarrhythmic activity in the adrenaline-induced arrhythmia, but no significant activity in the model of aconitine- or calcium chloride-induced arrhythmia. In addition, S-75 was not active in the model of post-reperfusion arrhythmias of the isolated rat hearts. Conversely, the compound showed therapeutic antiarrhythmic properties in adrenaline-induced arrhythmia, reducing post-arrhythmogen heart rhythm disorders, and decreasing animal mortality. Thus, we suggest that the blockade of α<sub>1</sub>-adrenoceptor might be beneficial in restoring normal heart rhythm in adrenaline-induced arrhythmia.Klaudia LustykKinga SałaciakPaula ZarębaAgata SiwekJacek SapaKarolina PytkaMDPI AGarticlearrhythmiaantiarrhythmic effectadrenaline-induced arrhythmiaα<sub>1</sub>-adrenoceptorα<sub>1</sub>-adrenolyticspyrrolidin-2-oneMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1065, p 1065 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
arrhythmia antiarrhythmic effect adrenaline-induced arrhythmia α<sub>1</sub>-adrenoceptor α<sub>1</sub>-adrenolytics pyrrolidin-2-one Medicine R Pharmacy and materia medica RS1-441 |
| spellingShingle |
arrhythmia antiarrhythmic effect adrenaline-induced arrhythmia α<sub>1</sub>-adrenoceptor α<sub>1</sub>-adrenolytics pyrrolidin-2-one Medicine R Pharmacy and materia medica RS1-441 Klaudia Lustyk Kinga Sałaciak Paula Zaręba Agata Siwek Jacek Sapa Karolina Pytka The Antiarrhythmic Activity of Novel Pyrrolidin-2-one Derivative S-75 in Adrenaline-Induced Arrhythmia |
| description |
Arrhythmia is a quivering or irregular heartbeat that can often lead to blood clots, stroke, heart failure, and other heart-related complications. The limited efficacy and safety of antiarrhythmic drugs require the design of new compounds. Previous research indicated that pyrrolidin-2-one derivatives possess an affinity for α<sub>1</sub>-adrenergic receptors. The blockade of α<sub>1</sub>-adrenoceptor may play a role in restoring normal sinus rhythm; therefore, we aimed to verify the antiarrhythmic activity of novel pyrrolidin-2-one derivative S-75. In this study, we assessed the influence on sodium, calcium, potassium channels, and β<sub>1</sub>-adrenergic receptors to investigate the mechanism of action of S-75. Lack of affinity for β<sub>1</sub>-adrenoceptors and weak effects on ion channels decreased the role of these adrenoceptors and channels in the pharmacological activity of S-75. Next, we evaluated the influence of S-75 on normal ECG in rats and isolated rat hearts, and the tested derivative did not prolong the QT<sub>c</sub> interval, which may confirm the lack of the proarrhythmic potential. We tested antiarrhythmic activity in adrenaline-, aconitine- and calcium chloride-induced arrhythmia models in rats. The studied compound showed prophylactic antiarrhythmic activity in the adrenaline-induced arrhythmia, but no significant activity in the model of aconitine- or calcium chloride-induced arrhythmia. In addition, S-75 was not active in the model of post-reperfusion arrhythmias of the isolated rat hearts. Conversely, the compound showed therapeutic antiarrhythmic properties in adrenaline-induced arrhythmia, reducing post-arrhythmogen heart rhythm disorders, and decreasing animal mortality. Thus, we suggest that the blockade of α<sub>1</sub>-adrenoceptor might be beneficial in restoring normal heart rhythm in adrenaline-induced arrhythmia. |
| format |
article |
| author |
Klaudia Lustyk Kinga Sałaciak Paula Zaręba Agata Siwek Jacek Sapa Karolina Pytka |
| author_facet |
Klaudia Lustyk Kinga Sałaciak Paula Zaręba Agata Siwek Jacek Sapa Karolina Pytka |
| author_sort |
Klaudia Lustyk |
| title |
The Antiarrhythmic Activity of Novel Pyrrolidin-2-one Derivative S-75 in Adrenaline-Induced Arrhythmia |
| title_short |
The Antiarrhythmic Activity of Novel Pyrrolidin-2-one Derivative S-75 in Adrenaline-Induced Arrhythmia |
| title_full |
The Antiarrhythmic Activity of Novel Pyrrolidin-2-one Derivative S-75 in Adrenaline-Induced Arrhythmia |
| title_fullStr |
The Antiarrhythmic Activity of Novel Pyrrolidin-2-one Derivative S-75 in Adrenaline-Induced Arrhythmia |
| title_full_unstemmed |
The Antiarrhythmic Activity of Novel Pyrrolidin-2-one Derivative S-75 in Adrenaline-Induced Arrhythmia |
| title_sort |
antiarrhythmic activity of novel pyrrolidin-2-one derivative s-75 in adrenaline-induced arrhythmia |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/919015ed90c64d18ab47d372690bf405 |
| work_keys_str_mv |
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