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

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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.

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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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Authors and Affiliations

  1. Department of Urology, Gemelli Hospital, Catholic University Medical School, Rome, Italy

    Emilio Sacco, Francesco Pinto & Pierfrancesco Bassi

  2. Urologia, Policlinico Gemelli, Largo A. Gemelli 8, 00168, Rome, Italy

    Emilio Sacco

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  1. Emilio Sacco
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  2. Francesco Pinto
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  3. Pierfrancesco Bassi
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Correspondence to Emilio Sacco.

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Sacco, E., Pinto, F. & Bassi, P. Emerging pharmacological targets in overactive bladder therapy: experimental and clinical evidences. Int Urogynecol J 19, 583–598 (2008). https://doi.org/10.1007/s00192-007-0529-z

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  • DOI: https://doi.org/10.1007/s00192-007-0529-z

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