Pharmacological evaluation of pyrrolidines as potent α1-adrenergic receptor antagonist with uro-selective profile

  • Jacek Sapa Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 Street, 30-688 Kraków, Poland
  • Marek Bednarski Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 Street, 30-688 Kraków, Poland
  • Leszek Nowiński Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 Street, 30-688 Kraków, Poland
  • Magdalena Kotańska Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 Street, 30-688 Kraków, Poland
  • Joanna Knutelska Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 Street, 30-688 Kraków, Poland
  • Paula Zaręba Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland
  • Anna Lechocka-Nowak Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 Street, 30-688 Kraków, Poland
  • Małgorzata Zygmunt Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 Street, 30-688 Kraków, Poland
  • Małgorzata Belczyk Department of Pharmacological Screening, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 Street, 30-688 Kraków, Poland

Abstract

Continuing our efforts in developing potent α1-adrenoceptor antagonists with uroselective profile, a series of derivatives of pyrrolidines was biologically evaluated in vitro for their affinity for α1- and α2-adrenoceptors. Result from binding assays allowed the identification of compounds with the highest affinity and selectivity for α1-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 α1A-adrenoceptor versus α1B 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 α1A-adrenoceptor antagonist with stronger uroselective profile, requires further research.

Published
2018-08-17
How to Cite
SAPA, Jacek et al. Pharmacological evaluation of pyrrolidines as potent α1-adrenergic receptor antagonist with uro-selective profile. Medicina Internacia Revuo - International Medicine Review, [S.l.], v. 28, n. 110, p. 23-33, aug. 2018. ISSN 0465-5435. Available at: <http://interrev.com/mir/index.php/mir/article/view/117>. Date accessed: 23 sep. 2018.
Section
Original publication