Treatment of the overactive bladder: possible central nervous system drug targets☆

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Abstract

The well-known side effects of antimuscarinic drugs have focused interest on other modalities of treatment of the overactive bladder. To effectively control bladder activity, identification of suitable targets for pharmacologic intervention is necessary. Such targets may be found in the central nervous system (CNS) or peripherally. Several CNS transmitters may modulate voiding, but few drugs with a defined CNS site of action have been developed for treatment of voiding disorders. Drugs affecting γ-aminobutyric acid, opioid, serotonin, noradrenaline, dopamine, or glutamatergic receptors and mechanisms are known to influence micturition, and potentially such drugs could be developed for clinical use. However, a selective action on the lower urinary tract may be difficult to obtain.

Section snippets

Central nervous system targets

Micturition in both humans and animals occurs in response to afferent signals from the lower urinary tract. In conscious animals, distention of the bladder wall is the primary stimulus. At least 2 types of afferent neurons innervate the urinary bladder. The first type is mechanosensitive, with myelinated axons, and is activated by both low (nonnociceptive) and high (nociceptive) intravesical pressure. The second type of afferents does not respond to bladder distention, possesses unmyelinated

Conclusion

To effectively control bladder activity, and to treat urinary incontinence caused by bladder overactivity, identification of suitable targets for pharmacologic intervention is necessary. In the CNS, drugs interfering with, for example, serotonin, noradrenaline, dopamine, or GABA mechanisms can modify the micturition reflex. Further investigations are needed to clarify the potential of these mechanisms as targets for drugs to treat overactive bladder.

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    ☆

    This study was supported by Grant No. 6837 from the Swedish Medical Research Council

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