Functional characterisation of the pharmacological profile of the putative alpha1B-adrenoceptor antagonist, (+)-cyclazosin.

We studied the functional pharmacological profile of (+)-cyclazosin, which has been characterised as a selective, high-affinity (pKi = 9.68) alpha1B-adrenoceptor ligand in binding experiments with rat liver membranes. The pKa/pA2 values for antagonism of contractions mediated via alpha1A/L-adrenoceptors of rat small mesenteric artery, alpha1B-adrenoceptors of rat aorta and alpha1B-adrenoceptors of rat spleen were 7.78 +/- 0.04, 6.86 +/- 0.07 and 7.96 +/- 0.08, respectively. Furthermore, in mouse spleen, which is also regarded as an alpha1B-adrenoceptor preparation, (+)-cyclazosin displayed low potency and did not act as a competitive antagonist. Thus, in contrast with results obtained in radioligand binding experiments, (+)-cyclazosin does not behave as a selective alpha1B-adrenoceptor antagonist in functional tissues. Whether this discrepancy has consequences for the classification of alpha1-adrenoceptors requires further investigation.