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Title: The mechanism of antiarrhythmic activity of the new pyrrolidin-2-one and methylazetidine derivatives

Author:

Lustyk, Klaudia

Date:

2019

Type:

Praca doktorska

Abstract:

The antiarrhythmic activity of the new pyrrolidin-2-one and methylazetidine derivatives was determined in this study and their mechanism of action was investigated. Most of the tested compounds showed affinity for α1-adrenergic receptors. The influence of studied derivatives on blood pressure response to methoxamine confirmed the antagonism against the α1-adrenergic receptors. None of the tested compounds prolonged the QTc interval, which may indicate a lack of proarrhythmic potential. Majority of tested compounds showed prophylactic antiarrhythmic activity in the adrenaline induced arrhythmia. Lack of affinity for β1-adrenergic receptors ultimately excluded the role of the β1-adrenolytic component in the mechanism of antiarrhythmic activity. None of the tested compounds restored the sinus rhythm and reduced the mortality in aconitine induced arrhythmia or showed significant activity in the model of calcium chloride induced arrhythmia. All compounds showed hypotensive activity, due to their α1-adrenolytic properties. AG-608 and S-75 were selected for extended studies. Both compounds showed weaker effects on calcium and potassium channels than reference compounds, which minimizes the contribution of these channels to their mechanism of action. AG-608 reduced the flow of sodium current stronger than dibukaine, which may confirm the participation of these channels in its antiarrhythmic activity. In addition, AG-608 showed activity in the model of post-reperfusion arrhythmias of the isolated rat hearts. Both compounds acted therapeutically in the adrenaline induced arrhythmia.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

farmakologia ; choroby układu krążenia

Degree grantor:

Uniwersytet Jagielloński. Collegium Medicum. Wydział Farmaceutyczny.

Promoter:

Jacek Sapa ; Karolina Pytka

Date issued:

2019

Format:

application/pdf

Identifier:

oai:dl.cm-uj.krakow.pl:4368

Call number:

ZB-131958

Access rights:

tylko w bibliotece

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum

Subject and keywords:

arrhythmia antiarrhythmic drugs α1-adrenolytics pyrrolidin-2-one methylazetidine

Object collections:

Last modified:

Nov 16, 2020

In our library since:

Aug 11, 2020

Number of object content hits:

1

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/4369

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Edition name Date
ZB-131958 Nov 16, 2020

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