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PHARMACOLOGICAL EVALUATION OF PYRROLIDINES AS POTENT ! 1 - ADRENERGIC RECEPTOR ANTAGONIST WITH URO-SELECTIVE PROFILE

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Sapa J., Bednarski M., Nowiński L., Kotańska M., Knutelska J., Zaręba P., LECHOCKA-NOWAK A., BELCZYK M., ZYGMUNT M.

Medicina Internacia Revuo

2018

vol. 28

issue 110

23-34

Continuing our efforts in developing potent α 1 -adrenoceptor antagonists with uroselective profile, a series of derivatives of pyrrolidines was biologically evaluated in vitro for their affinity for α 1 - and α 2 -adrenoceptors. Result from binding assays allowed the identification of compounds with the highest affinity and selectivity for α 1 -adrenoceptors behaving as potent antagonists at those sites in cellular functional assays. Among tested derivatives, compound V [1-(3-(4-(3- chlorophenyl)piperazin-1-yl)propyl)pyrrolidin-2-one], displayed a 152-fold functional preference to α 1A -adrenoceptor versus α 1B subtype. Finally, the most promising compound V at the doses of 2, 5 and 10 mg/kg after i.v. administered, in contrast to tamsulosin (at a dose of 2 mg/kg, i.v.) did not significantly decrease systolic and diastolic blood pressure in normotensive anesthetized rats. This selected α 1A -adrenoceptor antagonist with stronger uroselective profile, requires further research.

ANTIARRHYTHMIC AND HYPOTENSIVE ACTIVITY OF NEW ANALOGUES OF THEOPHYLLINE

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Sapa J., Zygmunt M., Krawczyk Ł., Dudek M., Bednarski M., Nowiński L., Knutelska J., Chłoń-Rzepa G., Pawłowski M.

Medicina Internacia Revuo

2013

vol. 25

issue 100

128-135

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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2 Medicina Internacia Revuo

1 2018

1 2013

2 Bednarski M.

2 Knutelska J.

2 Nowiński L.

2 Sapa J.

1 BELCZYK M.

1 Chłoń-Rzepa G.

1 Dudek M.

1 Kotańska M.

1 Krawczyk Ł.

1 LECHOCKA-NOWAK A.

1 Pawłowski M.

1 ZYGMUNT M.

1 Zaręba P.

1 Zygmunt M.

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PHARMACOLOGICAL EVALUATION OF PYRROLIDINES AS POTENT ! 1 - ADRENERGIC RECEPTOR ANTAGONIST WITH URO-SELECTIVE PROFILE

ANTIARRHYTHMIC AND HYPOTENSIVE ACTIVITY OF NEW ANALOGUES OF THEOPHYLLINE