Pharmacological Evaluation of the Effects of Phenylcarbamic Acid Derivatives on Cardiovascular Functions in Rats
Four phenylcarbamic acid derivatives, (1-(4-fluorophenyl)- 4-[3-(4-methoxyphenylcarbamoyloxy)-2-hydroxypropyl]piperazinium chloride (1), (1-(2-methylphenyl)-4-[3-(4-methoxyphenylcarbamoyloxy)- 2-hydroxypropyl]piperazinium chloride) (2), (1-(2-methylphenyl)-4-[3-(4-ethoxyphenylcarbamoyloxy)- 2-hydrox...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Sciendo
2018-12-01
|
| Series: | Acta Pharmaceutica |
| Subjects: | |
| Online Access: | https://doi.org/10.2478/acph-2018-0034 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832572299491934208 |
|---|---|
| author | Kralova Eva Racanska Eva Vicenova Anna Boselova Iveta Malik Ivan Stankovicova Tatiana |
| author_facet | Kralova Eva Racanska Eva Vicenova Anna Boselova Iveta Malik Ivan Stankovicova Tatiana |
| author_sort | Kralova Eva |
| collection | DOAJ |
| description | Four phenylcarbamic acid derivatives, (1-(4-fluorophenyl)- 4-[3-(4-methoxyphenylcarbamoyloxy)-2-hydroxypropyl]piperazinium chloride (1), (1-(2-methylphenyl)-4-[3-(4-methoxyphenylcarbamoyloxy)- 2-hydroxypropyl]piperazinium chloride) (2), (1-(2-methylphenyl)-4-[3-(4-ethoxyphenylcarbamoyloxy)- 2-hydroxypropyl]piperazinium chloride) (3) and (1-(3-trifluoromethylphenyl)-4-[3-(4-methoxyphenylcarbamoyloxy)- 2-hydroxypropyl]piperazinium chloride) (4) were investigated for their ability to affect various cardiovascular functions and to establish their chemical structure-biological activity relationship. The compounds were evaluated for their antiarrhythmic efficacy using ouabain-induced rhythm disturbances and the ability to inhibit the positive chronotropic effect of isoproterenol in isolated atria of Wistar rats. Electrocardiogram (ECG) parameters in isolated hearts of spontaneously hypertensive rats (SHR) perfused according to the Langendorff method and ability to decrease phenylephrine- -induced contraction of the aortic strips after repeated administration of the compounds were also analyzed. Only compound 3 delayed significantly the evaluated parameter of arrhythmogenicity and was able to antagonize the isoproterenol- induced positive chronotropic effect in normotensive rats’ atria. Similarly, in SHR rats, only compound 3 was able to decrease heart frequency significantly without influencing the duration of QT (time between the start of the Q wave and the end of the T wave) and QTc (frequency corrected QT) intervals. The evaluated endothelial function was improved after administration of compound 2. Fluorine-containing structures (1 and 4) were less effective compared to 2´-methylphenylpiperazine derivatives (2 and 3). The latter two compounds showed suitable efficacy, which supported their use for futher pharmacological research. |
| format | Article |
| id | doaj-art-bdf19405919a4d648069b5d5a537bea5 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2018-12-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-bdf19405919a4d648069b5d5a537bea52025-02-02T11:05:46ZengSciendoActa Pharmaceutica1846-95582018-12-0168450751510.2478/acph-2018-0034acph-2018-0034Pharmacological Evaluation of the Effects of Phenylcarbamic Acid Derivatives on Cardiovascular Functions in RatsKralova Eva0Racanska Eva1Vicenova Anna2Boselova Iveta3Malik Ivan4Stankovicova Tatiana5Comenius University in Bratislava Faculty of Pharmacy, Department of Pharmacology and ToxicologyBratislava, Slovak RepublicComenius University in Bratislava Faculty of Pharmacy, Department of Pharmacology and ToxicologyBratislava, Slovak RepublicComenius University in Bratislava Faculty of Pharmacy, Department of Pharmacology and ToxicologyBratislava, Slovak RepublicComenius University in Bratislava Faculty of Pharmacy, Department of Pharmacology and ToxicologyBratislava, Slovak RepublicComenius University in Bratislava Faculty of Pharmacy, Department of Pharmaceutical ChemistryBratislava, Slovak RepublicComenius University in Bratislava Faculty of Pharmacy, Department of Pharmacology and ToxicologyBratislava, Slovak RepublicFour phenylcarbamic acid derivatives, (1-(4-fluorophenyl)- 4-[3-(4-methoxyphenylcarbamoyloxy)-2-hydroxypropyl]piperazinium chloride (1), (1-(2-methylphenyl)-4-[3-(4-methoxyphenylcarbamoyloxy)- 2-hydroxypropyl]piperazinium chloride) (2), (1-(2-methylphenyl)-4-[3-(4-ethoxyphenylcarbamoyloxy)- 2-hydroxypropyl]piperazinium chloride) (3) and (1-(3-trifluoromethylphenyl)-4-[3-(4-methoxyphenylcarbamoyloxy)- 2-hydroxypropyl]piperazinium chloride) (4) were investigated for their ability to affect various cardiovascular functions and to establish their chemical structure-biological activity relationship. The compounds were evaluated for their antiarrhythmic efficacy using ouabain-induced rhythm disturbances and the ability to inhibit the positive chronotropic effect of isoproterenol in isolated atria of Wistar rats. Electrocardiogram (ECG) parameters in isolated hearts of spontaneously hypertensive rats (SHR) perfused according to the Langendorff method and ability to decrease phenylephrine- -induced contraction of the aortic strips after repeated administration of the compounds were also analyzed. Only compound 3 delayed significantly the evaluated parameter of arrhythmogenicity and was able to antagonize the isoproterenol- induced positive chronotropic effect in normotensive rats’ atria. Similarly, in SHR rats, only compound 3 was able to decrease heart frequency significantly without influencing the duration of QT (time between the start of the Q wave and the end of the T wave) and QTc (frequency corrected QT) intervals. The evaluated endothelial function was improved after administration of compound 2. Fluorine-containing structures (1 and 4) were less effective compared to 2´-methylphenylpiperazine derivatives (2 and 3). The latter two compounds showed suitable efficacy, which supported their use for futher pharmacological research.https://doi.org/10.2478/acph-2018-0034phenylcarbamic acid derivativesantiarrhythmic activityisolated atriaelectrical activityvascular contractilityrat |
| spellingShingle | Kralova Eva Racanska Eva Vicenova Anna Boselova Iveta Malik Ivan Stankovicova Tatiana Pharmacological Evaluation of the Effects of Phenylcarbamic Acid Derivatives on Cardiovascular Functions in Rats Acta Pharmaceutica phenylcarbamic acid derivatives antiarrhythmic activity isolated atria electrical activity vascular contractility rat |
| title | Pharmacological Evaluation of the Effects of Phenylcarbamic Acid Derivatives on Cardiovascular Functions in Rats |
| title_full | Pharmacological Evaluation of the Effects of Phenylcarbamic Acid Derivatives on Cardiovascular Functions in Rats |
| title_fullStr | Pharmacological Evaluation of the Effects of Phenylcarbamic Acid Derivatives on Cardiovascular Functions in Rats |
| title_full_unstemmed | Pharmacological Evaluation of the Effects of Phenylcarbamic Acid Derivatives on Cardiovascular Functions in Rats |
| title_short | Pharmacological Evaluation of the Effects of Phenylcarbamic Acid Derivatives on Cardiovascular Functions in Rats |
| title_sort | pharmacological evaluation of the effects of phenylcarbamic acid derivatives on cardiovascular functions in rats |
| topic | phenylcarbamic acid derivatives antiarrhythmic activity isolated atria electrical activity vascular contractility rat |
| url | https://doi.org/10.2478/acph-2018-0034 |
| work_keys_str_mv | AT kralovaeva pharmacologicalevaluationoftheeffectsofphenylcarbamicacidderivativesoncardiovascularfunctionsinrats AT racanskaeva pharmacologicalevaluationoftheeffectsofphenylcarbamicacidderivativesoncardiovascularfunctionsinrats AT vicenovaanna pharmacologicalevaluationoftheeffectsofphenylcarbamicacidderivativesoncardiovascularfunctionsinrats AT boselovaiveta pharmacologicalevaluationoftheeffectsofphenylcarbamicacidderivativesoncardiovascularfunctionsinrats AT malikivan pharmacologicalevaluationoftheeffectsofphenylcarbamicacidderivativesoncardiovascularfunctionsinrats AT stankovicovatatiana pharmacologicalevaluationoftheeffectsofphenylcarbamicacidderivativesoncardiovascularfunctionsinrats |