2-phenyl-1-(3-pyrrolidin-1-il-propyl)-1 H-indole hydrochloride (SS-68): Antiarrhythmic and cardioprotective activity and its molecular mechanisms of action (Part I)
Introduction. The problem of heart rhythm disturbances is one of the most urgent topics of modern cardiology. According to the currently available concepts, 1,2- and 1,3-disubstituted aminoindole derivatives, which compound 2-phenyl-1-(3-pyrrolidin-1-il-propyl)-1H-indole hydrochloride (SS-68) belong...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Belgorod National Research University
2018-06-01
|
| Series: | Research Results in Pharmacology |
| Online Access: | https://rrpharmacology.pensoft.net/article/28592/download/pdf/ |
| _version_ | 1797427650066644992 |
|---|---|
| author | Saida K. Bogus Pavel A. Galenko-Yaroshevsky Konstantin F. Suzdalev Galina V. Sukoyan Valery G. Abushkevich |
| author_facet | Saida K. Bogus Pavel A. Galenko-Yaroshevsky Konstantin F. Suzdalev Galina V. Sukoyan Valery G. Abushkevich |
| author_sort | Saida K. Bogus |
| collection | DOAJ |
| description | Introduction. The problem of heart rhythm disturbances is one of the most urgent topics of modern cardiology. According to the currently available concepts, 1,2- and 1,3-disubstituted aminoindole derivatives, which compound 2-phenyl-1-(3-pyrrolidin-1-il-propyl)-1H-indole hydrochloride (SS-68) belongs to, are a promising chemical group in terms of their cardio-pharmacological activity.
Materials and methods. To study the anti-arrhythmic activity of SS-68 compound, the following models were used: 1) Models of cardiogenic arrhythmia: aconitine-inducedic, calcium chloride-induced, barium chloride-induced, cesium chloride-induced, adrenaline model of arrhythmia, strophanthine-induced arrhythmias, as well as arrhythmias caused by electrostimulation and acute myocardial ischemia; 2) neurogenic arrhythmias: arrhythmias caused by administration of aconitine, strophanthine K, cesium chloride into the IV ventricle of the brain and also by applying carbachol on the somatosensory cortex. To assess the antianginal activity of SS-68 in various models, the effect of this drug and comparators on the intact and ischemic myocardium was studied.
Results. It was found that with cardiogenic arrhythmias, SS-68 compound exhibits a pronounced antiarrhythmic effect and brings to normal the electrophysiological pattern of the heart, in most cases exceeding the analogous effect of reference drugs (amiodarone, lidocaine, aymaline, ethacizine, etmozine, quinidine anaprilin). In neurogenic arrhythmias, SS-68 also had a stopping effect, and, in addition, reduced the epileptiform activity of the brain in the model with the application of carbachol on the somatosensory cortex. In the study of antianginal and coronary vasolidating activities, SS-68 demonstrated pronounced thrombolytic and anti-ischemic activities, manifested in an increase in the coronary blood flow, a positive effect on ST-segment depression, and a decrease in the area of necrosis in experimental myocardial infarction.
Discussion. The antiarrhythmic and antianginal activities of SS-68 compound create the prerequisites for further study of the pharmacological properties of this molecule. In addition, it seems appropriate to continue studying the pharmacodynamics, pharmacokinetics and molecular mechanisms of SS-68 action.
Conclusions. SS-68 compound is a promising pharmacological agent with a high activity towards various electrophysiological disorders in the heart, and, in addition, it has significant antiischemic and coronary vasolidating properties. |
| first_indexed | 2024-03-09T08:47:17Z |
| format | Article |
| id | doaj.art-89b4724e6b224bbdb0442c3eed441901 |
| institution | Directory Open Access Journal |
| issn | 2658-381X |
| language | English |
| last_indexed | 2024-03-09T08:47:17Z |
| publishDate | 2018-06-01 |
| publisher | Belgorod National Research University |
| record_format | Article |
| series | Research Results in Pharmacology |
| spelling | doaj.art-89b4724e6b224bbdb0442c3eed4419012023-12-02T15:09:54ZengBelgorod National Research UniversityResearch Results in Pharmacology2658-381X2018-06-014213315010.3897/rrpharmacology.4.28592285922-phenyl-1-(3-pyrrolidin-1-il-propyl)-1 H-indole hydrochloride (SS-68): Antiarrhythmic and cardioprotective activity and its molecular mechanisms of action (Part I)Saida K. Bogus0Pavel A. Galenko-Yaroshevsky1Konstantin F. Suzdalev2Galina V. Sukoyan3Valery G. Abushkevich4Kuban State Medical UniversityKuban State Medical UniversitySouthern Federal UniversityInternational Research Centre for Biophysics and of Introduction of New Biomedical TechnologiesKuban State Medical UniversityIntroduction. The problem of heart rhythm disturbances is one of the most urgent topics of modern cardiology. According to the currently available concepts, 1,2- and 1,3-disubstituted aminoindole derivatives, which compound 2-phenyl-1-(3-pyrrolidin-1-il-propyl)-1H-indole hydrochloride (SS-68) belongs to, are a promising chemical group in terms of their cardio-pharmacological activity. Materials and methods. To study the anti-arrhythmic activity of SS-68 compound, the following models were used: 1) Models of cardiogenic arrhythmia: aconitine-inducedic, calcium chloride-induced, barium chloride-induced, cesium chloride-induced, adrenaline model of arrhythmia, strophanthine-induced arrhythmias, as well as arrhythmias caused by electrostimulation and acute myocardial ischemia; 2) neurogenic arrhythmias: arrhythmias caused by administration of aconitine, strophanthine K, cesium chloride into the IV ventricle of the brain and also by applying carbachol on the somatosensory cortex. To assess the antianginal activity of SS-68 in various models, the effect of this drug and comparators on the intact and ischemic myocardium was studied. Results. It was found that with cardiogenic arrhythmias, SS-68 compound exhibits a pronounced antiarrhythmic effect and brings to normal the electrophysiological pattern of the heart, in most cases exceeding the analogous effect of reference drugs (amiodarone, lidocaine, aymaline, ethacizine, etmozine, quinidine anaprilin). In neurogenic arrhythmias, SS-68 also had a stopping effect, and, in addition, reduced the epileptiform activity of the brain in the model with the application of carbachol on the somatosensory cortex. In the study of antianginal and coronary vasolidating activities, SS-68 demonstrated pronounced thrombolytic and anti-ischemic activities, manifested in an increase in the coronary blood flow, a positive effect on ST-segment depression, and a decrease in the area of necrosis in experimental myocardial infarction. Discussion. The antiarrhythmic and antianginal activities of SS-68 compound create the prerequisites for further study of the pharmacological properties of this molecule. In addition, it seems appropriate to continue studying the pharmacodynamics, pharmacokinetics and molecular mechanisms of SS-68 action. Conclusions. SS-68 compound is a promising pharmacological agent with a high activity towards various electrophysiological disorders in the heart, and, in addition, it has significant antiischemic and coronary vasolidating properties.https://rrpharmacology.pensoft.net/article/28592/download/pdf/ |
| spellingShingle | Saida K. Bogus Pavel A. Galenko-Yaroshevsky Konstantin F. Suzdalev Galina V. Sukoyan Valery G. Abushkevich 2-phenyl-1-(3-pyrrolidin-1-il-propyl)-1 H-indole hydrochloride (SS-68): Antiarrhythmic and cardioprotective activity and its molecular mechanisms of action (Part I) Research Results in Pharmacology |
| title | 2-phenyl-1-(3-pyrrolidin-1-il-propyl)-1 H-indole hydrochloride (SS-68): Antiarrhythmic and cardioprotective activity and its molecular mechanisms of action (Part I) |
| title_full | 2-phenyl-1-(3-pyrrolidin-1-il-propyl)-1 H-indole hydrochloride (SS-68): Antiarrhythmic and cardioprotective activity and its molecular mechanisms of action (Part I) |
| title_fullStr | 2-phenyl-1-(3-pyrrolidin-1-il-propyl)-1 H-indole hydrochloride (SS-68): Antiarrhythmic and cardioprotective activity and its molecular mechanisms of action (Part I) |
| title_full_unstemmed | 2-phenyl-1-(3-pyrrolidin-1-il-propyl)-1 H-indole hydrochloride (SS-68): Antiarrhythmic and cardioprotective activity and its molecular mechanisms of action (Part I) |
| title_short | 2-phenyl-1-(3-pyrrolidin-1-il-propyl)-1 H-indole hydrochloride (SS-68): Antiarrhythmic and cardioprotective activity and its molecular mechanisms of action (Part I) |
| title_sort | 2 phenyl 1 3 pyrrolidin 1 il propyl 1 h indole hydrochloride ss 68 antiarrhythmic and cardioprotective activity and its molecular mechanisms of action part i |
| url | https://rrpharmacology.pensoft.net/article/28592/download/pdf/ |
| work_keys_str_mv | AT saidakbogus 2phenyl13pyrrolidin1ilpropyl1hindolehydrochloridess68antiarrhythmicandcardioprotectiveactivityanditsmolecularmechanismsofactionparti AT pavelagalenkoyaroshevsky 2phenyl13pyrrolidin1ilpropyl1hindolehydrochloridess68antiarrhythmicandcardioprotectiveactivityanditsmolecularmechanismsofactionparti AT konstantinfsuzdalev 2phenyl13pyrrolidin1ilpropyl1hindolehydrochloridess68antiarrhythmicandcardioprotectiveactivityanditsmolecularmechanismsofactionparti AT galinavsukoyan 2phenyl13pyrrolidin1ilpropyl1hindolehydrochloridess68antiarrhythmicandcardioprotectiveactivityanditsmolecularmechanismsofactionparti AT valerygabushkevich 2phenyl13pyrrolidin1ilpropyl1hindolehydrochloridess68antiarrhythmicandcardioprotectiveactivityanditsmolecularmechanismsofactionparti |