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.