Transient receptor potential channel modulators as pharmacological treatments for lower urinary tract symptoms (LUTS): myth or reality?

被引:27
作者
Deruyver, Yves [1 ,3 ,4 ]
Voets, Thomas [2 ,4 ]
De Ridder, Dirk [1 ,3 ,4 ]
Everaerts, Wouter [1 ,4 ,5 ]
机构
[1] Katholieke Univ Leuven, Dept Dev & Regenerat, Lab Expt Urol, B-3000 Louvain, Belgium
[2] Katholieke Univ Leuven, Dept Mol Cell Biol, Lab Ion Channel Res, B-3000 Louvain, Belgium
[3] Univ Hosp Leuven, Leuven, Belgium
[4] TRP Res Platform Leuven TRPLe, Leuven, Belgium
[5] Royal Melbourne Hosp, Melbourne, Vic, Australia
关键词
TRP channel; afferent nerve; urothelium; detrusor overactivity; LUTS; TRPV1; TRPV4; NEUROGENIC DETRUSOR OVERACTIVITY; ATTENUATES BLADDER OVERACTIVITY; DOUBLE-BLIND; INTRAVESICAL RESINIFERATOXIN; TRP CHANNELS; ION-CHANNEL; FUNCTIONAL EXPRESSION; CAPSAICIN RECEPTOR; MICTURITION REFLEX; COOLING REFLEX;
D O I
10.1111/bju.12876
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Transient receptor potential (TRP) channels belong to the most intensely pursued drug targets of the last decade. These ion channels are considered promising targets for the treatment of pain, hypersensitivity disorders and lower urinary tract symptoms (LUTS). The aim of the present review is to discuss to what extent TRP channels have adhered to their promise as new pharmacological targets in the lower urinary tract (LUT) and to outline the challenges that lie ahead. TRP vanilloid 1 (TRPV1) agonists have proven their efficacy in the treatment of neurogenic detrusor overactivity (DO), albeit at the expense of prolonged adverse effects as pelvic 'burning' pain, sensory urgency and haematuria. TRPV1 antagonists have been very successful in preclinical studies to treat pain and DO. However, clinical trials with the first generation TRPV1 antagonists were terminated early due to hyperthermia, a serious, on-target, side-effect. TRP vanilloid 4 (TRPV4), TRP ankyrin 1 (TRPA1) and TRP melastatin 8 (TRPM8) have important sensory functions in the LUT. Antagonists of these channels have shown their potential in pre-clinical studies of LUT dysfunction and are awaiting clinical validation.
引用
收藏
页码:686 / 697
页数:12
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