alpha(1)-adrenoceptor selectivity: The North American experience

Objective: The recent publication of multicentre US studies raises the poss ibility that the response to tamsulosin is dose-related and less than maxim um at 0.4 mg. The objective of the present study was to calculate pharmacol ogically equivalent, alpha-blocking doses of doxazosin and tamsulosin in a clinical setting and thereby to examine further the concept of 'uroselectiv ity' and 'prostate selectivity'. Methods: Healthy male volunteers were moni tored in controlled, crossover studies. The effects of placebo or alpha blo cker on phenylephrine (PE)-induced urethral and vascular responses, were de termined. These were related to plasma drug concentrations and used with in vitro radioligand binding data to derive receptor occupancy. Results: Doxa zosin effectively blocked PE-induced vascular and urethral changes over the dose range 1-16 mg. There was no evidence for tar get organ selectivity. T he degree of blockade of the PE induced responses by tamsulosin was highly dependent on the time of measurement, post drug administration. The degree of observed blockade with tamsulosin at 0.4 mg was substantially less than that observed at 0.8 mg tamsulosin and/or 1 mg doxazosin. Conclusions: Thes e studies provide no evidence of prostate selectivity for tamsulosin. 0.4 m g tamsulosin is a sub-optimal blocking dose and is equivalent to 1 mg of do xazosin and terazosin (1-2 mg), It is recommended that future comparative s tudies on benefit/risk in patients should include a range of doses encompas sing the ED50.