(+)-Cyclazosin, a selective α1B-adrenoceptor antagonist: Functional evaluation in rat and rabbit tissues

Abstract To shed light on the discrepancy between reported binding and functional affinity and selectivity at α 1b/B -adrenoceptors, the antagonist (+)-cyclazosin was reinvestigated in rat and rabbit tissues. It displayed a competitive antagonism at α 1A and α 1D -adrenoceptors of rat prostatic vas deferens and aorta with p A 2 values 7.75 and 7.27, respectively. In rabbit thoracic aorta (+)-cyclazosin competitively antagonized noradrenaline-induced contractions at α 1B -adrenoceptors with a p A 2 value of 8.85, whereas its affinity at α 1L -adrenoceptors was markedly lower (p A 2  = 6.75 − 7.09). In conclusion, these data confirmed that (+)-cyclazosin is a selective α 1B -adrenoceptor antagonist also in functional assays, showing 13- and 38-fold selectivity for the α 1B -adrenoceptor over α 1A - and α 1D -subtypes, respectively. Furthermore, (+)-cyclazosin displayed a significant selectivity for α 1B -adrenoceptors relative to the α 1L -subtype.