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