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Article

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden (K.-E.A.); and Division of Urology, University of Pennsylvania Health System, Philadelphia, Pennsylvania (A.J.W.)

Abstract

I. Introduction

II. Central Nervous System Targets

A. Central Nervous Control

B. Transmitter Systems

III. Peripheral Targets

A. Bladder

B. Urethra

IV. Effects of Sexual Hormones

A. Estrogen and Progesterone

B. Androgens

C. Pregnancy

V. Summary and Conclusions

The lower urinary tract constitutes a functional unit controlled by a complex interplay between the central and peripheral nervous systems and local regulatory factors. In the adult, micturition is controlled by a spinobulbospinal reflex, which is under suprapontine control. Several central nervous system transmitters can modulate voiding, as well as, potentially, drugs affecting voiding; for example, noradrenaline, GABA, or dopamine receptors and mechanisms may be therapeutically useful. Peripherally, lower urinary tract function is dependent on the concerted action of the smooth and striated muscles of the urinary bladder, urethra, and periurethral region. Various neurotransmitters, including acetylcholine, noradrenaline, adenosine triphosphate, nitric oxide, and neuropeptides, have been implicated in this neural regulation. Muscarinic receptors mediate normal bladder contraction as well as at least the main part of contraction in the overactive bladder. Disorders of micturition can roughly be classified as disturbances of storage or disturbances of emptying. Failure to store urine may lead to various forms of incontinence, the main forms of which are urge and stress incontinence. The etiology and pathophysiology of these disorders remain incompletely known, which is reflected in the fact that current drug treatment includes a relatively small number of more or less well-documented alternatives. Antimuscarinics are the main-stay of pharmacological treatment of the overactive bladder syndrome, which is characterized by urgency, frequency, and urge incontinence. Accepted drug treatments of stress incontinence are currently scarce, but new alternatives are emerging. New targets for control of micturition are being defined, but further research is needed to advance the pharmacological treatment of micturition disorders.