Trends in the Development of New Drugs for Treatment of Benign Prostatic Hyperplasia

Katarzyna      Kulig; Barbara      Malawska

Abstract

Benign prostatic hyperplasia (BPH) is a common condition in aging men that is characterized bynonmalignant enlargement of the prostate gland, and is frequently accompanied by urinary obstruction, andlower urinary tract symptoms (LUST). Currently pharmacotherapy of BPH is based on two classes of drugs: α1-adrenoceptor (α1-AR) antagonists and α5-reductase inhibitors. It has been shown that α1-AR antagonistsreduce symptom scores and increase peak urinary flow rates in BPH. Of particular importance for BPH therapyare uroselective α1-AR antagonists for which the hypotensive related side-effect caused by α1-AR blockade isreduced. α5-Reductase inhibitors reduce prostate volume and symptom scores, while increasing peak urinaryflow rates. This review describes new α1-AR antagonists and 5α-reductase inhibitors in the treatment of BPH.The new α1-AR antagonists represent various structures such as quinazolines, phenylethylamines, piperidines,and arylpiperazines.5α-Redu ctase inhibitors are classified into two groups: steroidal and non-steroidal. Thenewer non-steroidal inhibitors include derivatives of benzo[c]quinolizinones, benzo[f]quinolonones,piperidones and carboxylic acids. Besides the development of new compounds belonging to the abovementioned groups, new agents for BPH treatment are sought among combined 5α-reductase/α1-AR inhibitors,endothelins, androgen receptors antagonists, growth factors, estrogens and phosphodiesterase isoenzymes aswell as several phytomedicines, used for prevention and treatment of prostate disorders. These new agents canbe used for the design of future targets and development of new drugs in the treatment of BPH. The discoveryof a number of active leads may also ultimately help in developing new safe and effective drugs.

Keywords: Benign prostatic hyperplasia, a1α-adrenoceptor antagonists, 5α-reductase inhibitors

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