The challenge of overactive bladder therapy: alternative to antimuscarinic agents

Abstract

Contemporary, the management of overactive bladder (OAB), a medical condition characterized by urgency, with or without urge urinary incontinence, frequency and nocturia, in absence of genitourinary pathologies or metabolic factors that could explain these symptoms, is complex, and a wide range of conservative treatments has been offered, including bladder training, biofeedback, behavioral changes, oral or intravesical anticholinergic agents, S3 sacral neuromodulation and peripheral electrical stimulation. Clinical efficacy of these treatments remains an open issue and several experimental and clinical studies were carried out in the last years improving the results of medical treatment. Here we review the pathophysiology of micturition reflex, the current therapies for OAB and the rationale for alternative treatments. Furthermore we critically address the potential use of medications targeting the central nervous system (CNS) and the primary sensory nerves of the bladder wall, we review the use of agonists of nociceptin/orphanin protein (NOP) receptor and finally we report the results obtained by intradetrusor injection of botulinum toxin.

Involvement of 5-HT3receptors in pudendal inhibition of bladder overactivity in cats

“…OAB-related costs add up to around $12.6 billion per year (21). Antimuscarinic drugs are currently the first line of therapy, but their adverse effects and poor efficacy result in a high patient dropout rate (1,2,16). Sacral neuromodulation (InterStim, Medtronic, Minneapolis, MN) is an effective US Food and Drug Administration-approved alternative for patients with refractory OAB (34), and recent studies (22,23) have suggested that pudendal neuromodulation is superior to sacral neuromodulation.…”

“…Ondansetron (a 5-HT 3 receptor antagonist) and naloxone (an opioid receptor antagonist) were administered intravenously to determine the role of these receptors in the PNS inhibition of bladder overactivity. Understanding the neurotransmitter mechanisms underlying neuromodulation therapies is important for the development of new drugs or improvement of current neuromodulation therapies for OAB (1,2,16).…”

Controversy over the pharmacological treatments of storage symptoms in spinal cord injury patients: a literature overview

“…Neurophysiological achievements seem to support a new hyper-afferent activity as the main changes in neurogenic bladder. 7 Theoretically, it should be possible to delay the reflex voiding, increasing bladder capacity without interfering with the contractile phase during bladder emptying.…”

“…6 Over the past years, research has focused on this system to develop new drugs for the treatment of NLUTS and several new pharmacological achievements have been obtained. 7 Table 1 summarises the main steps. Finally, Birder 8 showed that the urothelial cells exhibit 'neuronal-like' properties, similar to mechanosensitive and nociceptive sensory nerves, by release of neuromediators ( Figure 2).…”

Comparison between imipramine and imipramine combined with pseudoephedrine in 5–12-year-old children with uncomplicated enuresis: A double-blind clinical trial

“…The sympathetic system originates in the thoracolumbar cord (Th11eL2) and provides an inhibitory input to the bladder by the postganglionic nerve terminal release of norepinephrine, which excites b3 receptors in the body of the detrusor leading to bladder relaxation. The sympathetic system also provides an excitatory input to the urethral smooth muscle by the postganglionic nerve terminal release of norepinephrine which excites a1 receptors in the urethra leading to urethral closure [4]. Oral administration of pseudoephedrine, a stereoisomer of ephedrine that is a non-cathecholamine sympathomimetic agent, enhances release of norepinephrine from sympathetic neurons and directly stimulates both alpha and beta adrenoceptors [6].…”