Effect of tamsulosin, a novel α1‐adrenoceptor antagonist, on urethral pressure profile in anaesthetized dogs

The effect of tamsulosin (YM617, (R)(–)‐5‐[2‐[[2‐(o‐ethoxyphenoxy)ethyl]amino]propyl]‐2‐methoxybenzenesulfonamide HCl), a potent and selective α1‐adrenoceptor antagonist, was examined on urethral pressure profile (UPP) and mean arterial blood pressure (MBP) in pentobarbital anaesthetized male dogs. Selective α1‐adrenoceptor antagonists tamsulosin (1–100 μg kg–1 i.v.), prazosin (1–100 μg kg–1 i.v.) and bunazosin (1–100 μg kg–1 i.v.) produced a dose dependent reduction in prostatic pressure in the UPP. Doses required to reduce prostatic pressure in UPP by 30% were 3.6 ± 0.8 (n = 8), 6.9 ± 1.5 (n = 8) and 4.6 ± 0.9 (n = 8) μg kg–1 i.v., respectively. At the highest dose, tamsulosin exerted less hypotensive effect than prazosin and bunazosin. The calcium antagonist nicardipine (0.1–10 μg kg–1 i.v.) and angiotensin converting enzyme inhibitor captopril (10–1,000 μg kg–1 i.v.) reduced MBP in a dose dependent manner, but exerted no effect on prostatic pressure in the UPP. The diuretic trichloromethiazide (1–100 μg kg–1 i.v.) exerted no effect on UPP or MBP. Treatment with nicardipine (3 μg kg–1 i.v.), captopril (100 μg kg–1 i.v.) or trichlormethiazide (100 μg kg–1 i.v.) did not affect relaxant effect of tamsulosin on prostatic pressure in UPP, or potentiate its hypotensive effect. These results suggest that the α1‐adrenoceptor regulates urethral pressure as well as blood pressure in anaesthetized dogs, and that α1‐adrenoceptor antagonists may be useful in the treatment of micturition disorders associated with benign prostatic hyperplasia. In addition, as tamsulosin decreased urethral pressure with less hypotension, and as its effect was not influenced by treatment with hypotensive drugs, it may be a useful drug for the treatment of micturition disorders with few cardiovascular side effects.