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International Urogynecology Journal

, Volume 19, Issue 4, pp 583–598 | Cite as

Emerging pharmacological targets in overactive bladder therapy: experimental and clinical evidences

  • Emilio SaccoEmail author
  • Francesco Pinto
  • Pierfrancesco Bassi
Review Article

Abstract

Antimuscarinics are the mainstay of the medical therapy for overactive bladder, but their side effects and often modest success have prompted studies on novel pharmacological approaches. In this paper, we give a systematic literature review of peer-reviewed papers on the subject. Effective nonantimuscarinic treatments are currently scarce, but many new promising compounds are emerging, which target key molecular pathways involved in micturition control. The most promising potential therapeutic targets include: nervous GABAergic, glycinergic, dopaminergic, and serotonergic systems; b-adrenoceptors and cAMP metabolism; nonadrenergic–noncholinergic mechanisms such as purinergic and neuropeptidergic systems; vanilloid receptors; bladder afferent nerves; nonneuronal bladder signaling systems including urothelium and interstitial cells; prostanoids; Rho-kinase; and different subtypes of potassium and calcium channels. Despite the enormous amount of new biologic insight, very few drugs with mechanism of action other than antimuscarinics have passed as yet the proof-of-concept stage. Further preclinical and clinical studies are urgently needed in this rapidly moving field.

Keywords

Bladder Detrusor overactivity Pharmacological targets Urinary incontinence 

Abbreviations

5-HT

5-hydroxytryptamine

ACh

acetylcholine

AR

adrenoreceptor

ATP

adenosine 5′-triphosphate

BOO

bladder outlet obstruction

BPH

benign prostate hyperplasia

BTX

botulinum toxin

cAMP

3′-5′-cyclic adenosine monophosphate

CNS

central nervous system

COX

cyclooxygenase

DO

detrusor overactivity

ENK

enkephalin

GABA

gamma-aminobutyric acid

GAT

GABA transporter

HBSM

human bladder smooth muscle

i.a.

intrarteriuos

i.c.v.

intracerebroventricular

i.t.

intratecal

i.v.

intravenous

ICS

International Continence Society

ICs

interstitial cells

IDO

idiopathic detrusor overactivity

KCO

potassium channel opener

NANC

nonadrenergic noncholinergic

NDO

neurogenic detrusor overactivity

NK

neurokinin

NSAIDs

nonsteroidal antiinflammatory drugs

OAB

overactive bladder

PDE

phosphodiesterase

PG

prostaglandin

ROCK

Rho-kinase

RyR

ryanodine receptor

s.c.

subcutaneous

SP

substance P

SSRIs

selective serotonin reuptake inhibitors

TK

tachykinin

TRPV1

transient receptor potential vanilloid 1

TX

thromboxane

VDCC

voltage-dependent L-type Ca2+ channel

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Copyright information

© International Urogynecology Journal 2007

Authors and Affiliations

  • Emilio Sacco
    • 1
    • 2
    Email author
  • Francesco Pinto
    • 1
  • Pierfrancesco Bassi
    • 1
  1. 1.Department of Urology, Gemelli HospitalCatholic University Medical SchoolRomeItaly
  2. 2.UrologiaPoliclinico GemelliRomeItaly

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