Med.Inter.Rev. 2013, 100, 129-136.

Antiarrhythmic and hypotensive activity of new analogues of theophylline


Jacek Sapa1., Małgorzata Zygmunt1., Łukasz Krawczyk1., Marek Bednarski1., Joanna Knutelska1., Magdalena Dudek2., Leszek Nowiński2., Grażyna Chłoń-Rzepa3., Maciej Pawłowski3.

1.Zakład Wstępnych Badań Farmakologicznych Katedry Farmakodynamiki, Wydział Farmacji, Collegium Medicum Uniwersytetu Jagiellońskiego, Medyczna 9, 30-688 Kraków, Polska
2.Katedra Farmakodynamiki, Wydział Farmacji, Collegium Medicum Uniwersytetu Jagiellońskiego Medyczna 9, 30-688 Kraków, Polska
3.Katedra Chemii Farmaceutycznej, Wydział Farmacji, Collegium Medicum Uniwersytetu Jagiellońskiego Medyczna 9, 30-688 Kraków, Polska


Abstract

On the basis of our earlier studies in the group of 7,8-disubstituted derivatives of 1,3-dimetyl-3,7-dihydro-purine-2,6-dione, some new derivatives of theophylline were synthesized and tested for their electrocardiographic, antiarrhythmic and hypotensive activity as well as for α1-adrenoreceptor affinities. The performed preliminary tests indicated that new compounds did not significantly affect the normal ECG in vivo. As the result of present studies it may be concluded that all compounds did not possess hypotensive and arrhythmic activity. The results of the binding assays on α1-adrenergic receptors showed, that these derivatives display no affinity for α1-adrenergic receptors. Lack of antiarrhythmic and antihypertensive activity may result from the absence of affinity for the α1-adrenergic receptor. Performed chemical modifications lead to the loss of pharmacological activity previously observed among other derivatives in this group. Generally in comparison with the previously reported derivatives, replacing the phenoxyethylpiperazine by other moiety, changed the antiarrhythmic and hypotensive activity.

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Keywords: theophylline antiarrhythmic activity, hypotensive activity


Original language: Polish

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