(+)-Cyclazosin, a selective alpha1B-adrenoceptor antagonist: Functional evaluation in rat and rabbit tissues

To shed light on the discrepancy between reported binding and functional affinity and selectivity at α1b/B-adrenoceptors, the antagonist (+)-cyclazosin was reinvestigated in rat and rabbit tissues. It displayed a competitive antagonism at α1A and α1D-adrenoceptors of rat prostatic vas deferens and aorta with pA2 values 7.75 and 7.27, respectively. In rabbit thoracic aorta (+)-cyclazosin competitively antagonized noradrenaline-induced contractions at α1B-adrenoceptors with a pA2 value of 8.85, whereas its affinity at α1L-adrenoceptors was markedly lower (pA2=6.75−7.09). In conclusion, these data confirmed that (+)-cyclazosin is a selective α1B-adrenoceptor antagonist also in functional assays, showing 13- and 38-fold selectivity for the α1B-adrenoceptor over α1A- and α1D-subtypes, respectively. Furthermore, (+)-cyclazosin displayed a significant selectivity for α1B-adrenoceptors relative to the α1L-subtype.