Literature DB >> 21410684

Novel drug targets for the pharmacotherapy of benign prostatic hyperplasia (BPH).

S Ventura1, V l Oliver, C W White, J H Xie, J M Haynes, B Exintaris.   

Abstract

Benign prostatic hyperplasia (BPH) is the major cause of lower urinary tract symptoms in men aged 50 or older. Symptoms are not normally life threatening, but often drastically affect the quality of life. The number of men seeking treatment for BPH is expected to grow in the next few years as a result of the ageing male population. Estimates of annual pharmaceutical sales of BPH therapies range from $US 3 to 10 billion, yet this market is dominated by two drug classes. Current drugs are only effective in treating mild to moderate symptoms, yet despite this, no emerging contenders appear to be on the horizon. This is remarkable given the increasing number of patients with severe symptoms who are required to undergo invasive and unpleasant surgery. This review provides a brief background on prostate function and the pathophysiology of BPH, followed by a brief description of BPH epidemiology, the burden it places on society, and the current surgical and pharmaceutical therapies. The recent literature on emerging contenders to current therapies and novel drug targets is then reviewed, focusing on drug targets which are able to relax prostatic smooth muscle in a similar way to the α(1) -adrenoceptor antagonists, as this appears to be the most effective mechanism of action. Other mechanisms which may be of benefit are also discussed. It is concluded that recent basic research has revealed a number of novel drug targets such as muscarinic receptor or P2X-purinoceptor antagonists, which have the potential to produce more effective and safer drug treatments.
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

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Year:  2011        PMID: 21410684      PMCID: PMC3130937          DOI: 10.1111/j.1476-5381.2011.01332.x

Source DB:  PubMed          Journal:  Br J Pharmacol        ISSN: 0007-1188            Impact factor:   8.739


  182 in total

1.  An immunohistochemical and pharmacological study of tachykinins in the rat and guinea-pig prostate glands.

Authors:  S Buljubasich; W A Lau; J N Pennefather; S Ventura
Journal:  Eur J Pharmacol       Date:  1999-09-10       Impact factor: 4.432

2.  Phosphodiesterase type 5 inhibitors for the treatment of male lower urinary tract symptoms.

Authors:  Steven A Kaplan; Ricardo R Gonzalez
Journal:  Rev Urol       Date:  2007

3.  Characterization and functional relevance of cyclic nucleotide phosphodiesterase isoenzymes of the human prostate.

Authors:  S Uckert; A Küthe; U Jonas; C G Stief
Journal:  J Urol       Date:  2001-12       Impact factor: 7.450

4.  LHRH antagonist Cetrorelix reduces prostate size and gene expression of proinflammatory cytokines and growth factors in a rat model of benign prostatic hyperplasia.

Authors:  Ferenc G Rick; Andrew V Schally; Norman L Block; Gabor Halmos; Roberto Perez; Jesus B Fernandez; Irving Vidaurre; Luca Szalontay
Journal:  Prostate       Date:  2010-10-13       Impact factor: 4.104

5.  The efficacy of drugs for the treatment of LUTS/BPH, a study in 6 European countries.

Authors:  Annie Hutchison; Richard Farmer; Katia Verhamme; Richard Berges; Remigio Vela Navarrete
Journal:  Eur Urol       Date:  2006-06-27       Impact factor: 20.096

6.  Adenosine 5'-triphosphate and noradrenaline are excitatory cotransmitters to the fibromuscular stroma of the guinea pig prostate gland.

Authors:  Rosanda Buljubasich; Sabatino Ventura
Journal:  Eur J Pharmacol       Date:  2004-09-24       Impact factor: 4.432

7.  Interstitial cells in the human prostate: a new therapeutic target?

Authors:  Frank Van der Aa; Tania Roskams; Wim Blyweert; Dirk De Ridder
Journal:  Prostate       Date:  2003-09-01       Impact factor: 4.104

8.  A possible role of decreased relaxation mediated by beta-adrenoceptors in bladder outlet obstruction by benign prostatic hyperplasia.

Authors:  T Tsujii; H Azuma; T Yamaguchi; H Oshima
Journal:  Br J Pharmacol       Date:  1992-11       Impact factor: 8.739

9.  Responses to the antagonistic analog of LH-RH (SB-75, Cetrorelix) in patients with benign prostatic hyperplasia and prostatic cancer.

Authors:  D Gonzalez-Barcena; M Vadillo-Buenfil; F Gomez-Orta; M Fuentes Garcia; I Cardenas-Cornejo; A Graef-Sanchez; A M Comaru-Schally; A V Schally
Journal:  Prostate       Date:  1994       Impact factor: 4.104

10.  Peptidergic innervation of the human prostate, seminal vesicle and vas deferens.

Authors:  H Tainio
Journal:  Acta Histochem       Date:  1995-01       Impact factor: 2.479

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  23 in total

1.  Smooth muscle contraction and growth of stromal cells in the human prostate are both inhibited by the Src family kinase inhibitors, AZM475271 and PP2.

Authors:  Yiming Wang; Christian Gratzke; Alexander Tamalunas; Beata Rutz; Anna Ciotkowska; Frank Strittmatter; Annika Herlemann; Sophie Janich; Raphaela Waidelich; Chunxiao Liu; Christian G Stief; Martin Hennenberg
Journal:  Br J Pharmacol       Date:  2016-11-01       Impact factor: 8.739

2.  What makes the α(1A)-adrenoceptor gene express the α(1L)-adrenoceptor functional phenotype?

Authors:  Sabatino Ventura
Journal:  Br J Pharmacol       Date:  2012-03       Impact factor: 8.739

3.  Factors influencing biased agonism in recombinant cells expressing the human α1A -adrenoceptor.

Authors:  Edilson Dantas da Silva Junior; Masaaki Sato; Jon Merlin; Natalie Broxton; Dana S Hutchinson; Sabatino Ventura; Bronwyn A Evans; Roger J Summers
Journal:  Br J Pharmacol       Date:  2017-06-10       Impact factor: 8.739

Review 4.  What makes the α1A -adrenoceptor gene product assume an α1L -adrenoceptor phenotype?

Authors:  Carl W White; Edilson Dantas da Silva Junior; Linzi Lim; Sabatino Ventura
Journal:  Br J Pharmacol       Date:  2019-03-27       Impact factor: 8.739

5.  Pharmacokinetic bioequivalence studies of a fixed-dose combination of tamsulosin and dutasteride in healthy volunteers.

Authors:  Michael J Fossler; David A Collins; Meg M Thompson; Antonio Nino; Joseph J Bianco; Dushen Chetty
Journal:  Clin Drug Investig       Date:  2014-05       Impact factor: 2.859

6.  Inhibition of human prostate smooth muscle contraction by the LIM kinase inhibitors, SR7826 and LIMKi3.

Authors:  Qingfeng Yu; Christian Gratzke; Yiming Wang; Annika Herlemann; Christian Maximilian Sterr; Beata Rutz; Anna Ciotkowska; Xiaolong Wang; Frank Strittmatter; Christian G Stief; Martin Hennenberg
Journal:  Br J Pharmacol       Date:  2018-04-29       Impact factor: 8.739

7.  Combination treatment with naftopidil increases the efficacy of radiotherapy in PC-3 human prostate cancer cells.

Authors:  Yoichi Iwamoto; Kenichiro Ishii; Hideki Kanda; Manabu Kato; Manabu Miki; Shinya Kajiwara; Kiminobu Arima; Taizo Shiraishi; Yoshiki Sugimura
Journal:  J Cancer Res Clin Oncol       Date:  2017-02-27       Impact factor: 4.553

8.  A NAV2729-sensitive mechanism promotes adrenergic smooth muscle contraction and growth of stromal cells in the human prostate.

Authors:  Qingfeng Yu; Christian Gratzke; Ruixiao Wang; Bingsheng Li; Paul Kuppermann; Annika Herlemann; Alexander Tamalunas; Yiming Wang; Beata Rutz; Anna Ciotkowska; Xiaolong Wang; Frank Strittmatter; Raphaela Waidelich; Christian G Stief; Martin Hennenberg
Journal:  J Biol Chem       Date:  2019-06-26       Impact factor: 5.157

9.  Shrinkage of experimental benign prostatic hyperplasia and reduction of prostatic cell volume by a gastrin-releasing peptide antagonist.

Authors:  Ferenc G Rick; Andrew Abi-Chaker; Luca Szalontay; Roberto Perez; Miklos Jaszberenyi; Arumugam R Jayakumar; Nagarajarao Shamaladevi; Karoly Szepeshazi; Irving Vidaurre; Gabor Halmos; Awtar Krishan; Norman L Block; Andrew V Schally
Journal:  Proc Natl Acad Sci U S A       Date:  2013-01-28       Impact factor: 11.205

10.  Activation of innate anti-viral immune response genes in symptomatic benign prostatic hyperplasia.

Authors:  A A Madigan; K M Sobek; J L Cummings; W R Green; D J Bacich; D S O'Keefe
Journal:  Genes Immun       Date:  2012-09-06       Impact factor: 2.676

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