Silodosin and tadalafil have synergistic inhibitory effects on nerve-mediated contractions of human and rat isolated prostates

Roberta Buono, Alberto Briganti, Massimo Freschi, Luca Villa, Giovanni La Croce, Marco Moschini, Fabio Benigni, Fabio Castiglione, Francesco Montorsi, Petter Hedlund

Research output: Contribution to journalArticlepeer-review

Abstract

Lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) are associated with erectile dysfunction. Alpha-1-adrenoceptor antagonists are effective drugs for treating symptomatic BPH. Clinical data show improvements in LUTS by phosphodiesterase 5 inhibitors. This study aimed to evaluate effects of silodosin, a highly selective α1A-adrenoceptor antagonist, alone or in combination with the phosphodiesterase 5 inhibitor tadalafil on contractions of isolated human and rat prostates. In organbath studies, effects of increasing concentrations of silodosin (1 nM-1 μM) and tadalafil (100 nM-100 μM) on contractions by electrical field stimulation or phenylephrine of human and rat prostate strip preparations were investigated. The combination silodosin and tadalafil reduced electrically-induced contractions of human prostate preparations better than single drugs alone. At any frequencies (1-32 Hz), inhibitory effects of combined therapy (P-values vs single drug) in human tissue were 26-42% (1 nM silodosin+100 nM tadalafil; P1A-adrenoceptor antagonist and a phosphodiesterase 5 inhibitor for symptomatic BPH and suggests that the drug combination requires endogenous nerve-activity for optimal effect.

Original languageEnglish
Pages (from-to)42-51
Number of pages10
JournalEuropean Journal of Pharmacology
Volume744
DOIs
Publication statusPublished - Dec 5 2014

Keywords

  • Alfa-1A-adrenoceptor
  • Contraction
  • Inhibition
  • Phosphodiesterase 5
  • Prostate
  • Smooth muscle

ASJC Scopus subject areas

  • Pharmacology
  • Medicine(all)

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