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

• Authors: Jacek Sapa , Marek Bednarski , Leszek Nowiński , Magdalena Kotańska , Joanna Knutelska , Paulina Zaręba , Anna LECHOCKA-NOWAK , Małgorzata BELCZYK , Małgorzata ZYGMUNT
• Languages of publication: EN EO

Abstracts

EN

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.

Keywords

EN

derivatives of pyrrolidines; uroselective activity; α1-adrenoceptors antagonists; α1A/B receptorselectivity

Discipline

• PHARMACOLOGY: PHARMACOLOGY

• Journal: Medicina Internacia Revuo
• Year: 2018
• Volume: 28
• Issue: 110
• Pages: 23-34

Contributors

author

Jacek Sapa

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Marek Bednarski

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Leszek Nowiński

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Magdalena Kotańska

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Joanna Knutelska

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Paulina Zaręba

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Anna LECHOCKA-NOWAK

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Małgorzata BELCZYK

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Małgorzata ZYGMUNT

• Jagiellonian University Medical College, Faculty of Pharmacy Department of Pharmacological Screening,

• Document Type: article