James R. Docherty

Background RS17053 is classed as an α 1A ‐adrenoceptor selective antagonist. Objectives We have examined its profile of action at all subtypes of α 1 ‐adrenoceptor. Methods Noradrenaline (NA) evoked contractions of rat vas deferens involve α 1D ‐adrenoceptors in phasic contractions and α 1A ‐adrenoceptors in tonic contractions. Contractions of rat aorta to NA involve α 1D ‐ and α 1B ‐adrenoceptors. Results RS17053 (10 −5 M) shifted NA potency and virtually abolished tonic contractions to NA, with little or limited effect on phasic contractions. The α 1D ‐adrenoceptor antagonist BMY7378 (3 × 10 −7 M) significantly inhibited the remaining phasic component of the contractions, and the α 1A ‐adrenoceptor antagonist RS100329 (10 −7 M) inhibited further the residual tonic contraction. Hence, RS17053 shows high selectivity for α 1A ‐adrenoceptors over α 1D ‐adrenoceptors in rat vas deferens. However, RS17053 (10 −5 M) produced a large shift in the potency of NA in rat aorta, with a pK B of 6.82. Large shifts of NA potency in rat aorta involve α 1B ‐adrenoceptor blockade. Conclusion Results in rat vas deferens demonstrate low potency of RS17053 at α 1D ‐adrenoceptors, but results from rat aorta can only be explained as demonstrating α 1B ‐adrenoceptor antagonism by RS17053. RS17053 may be a useful pharmacological tool when reclassified as a mainly α 1A ‐ and to a lesser extent α 1B ‐adrenoceptor antagonist with little effect at α 1D ‐adrenoceptors.