新規α_1受容体遮断薬, 塩酸タムスロシンの研究開発

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Benign prostatic hyperplasia (BPH) is an age-related disorder characterized by urinary outlet obstruction. This obstruction is due to both mechanical compression of the urethra by the hypertrophied prostate and to functional contraction of the prostate and urethra by sympathetic stimulation. We invented a novel compound tamsulosin hydrochloride, a sulphamoyl-phenethylamine derivative which possesses potent and selective α_1-antagonism, and showed that this compound selectively reduced the intra-urethral pressure in the prostatic segment of the urethra in vivo. We also found that the α_1-adrenoceptor plays an important functional role in the prostate and urethra. For clinical use, a control release formulation was developed. This formulation did not induce orthostatic hypotension and could be administered at a fixed dose. A placebo-controlled double-blind dose finding study resulted in 0.2mg/d as the optimal dose. This formulation significantly improved urinary outlet obstruction without affecting blood pressure as compared with placebo in P-III study, and was approved in 1993 for use in the treatment of bladder outlet obstruction associated with BPH. Tamsulosin hydrochloride is the first α_1-antagonist which improves bladder outlet obstruction associated with BPH without affecting blood pressure, and the treatment can be initiated and maintained at a fixed dose. Recently, the α_1-adrenoceptor subtypes α_<1A>, α_<1B> and α_<1C> were identified. The α_<1C> subtype is predominant and plays an important role in the human prostate. Tamsulosin hydrochloride shows high selectivity for this subtype, further supporting the clinical findings that tamsulosin hydrochloride improves bladder outlet obstruction associated with BPH with no effect on the cardiovascular system.
公益社団法人日本薬学会の論文
1995-10-25

新規α_1受容体遮断薬, 塩酸タムスロシンの研究開発

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