Cizolirtine Citrate Is Safe and Effective for Treating Urinary Incontinence Secondary to Overactive Bladder: A Phase 2 Proof-of-Concept Study

Zát'ura, F; Všetiča, Jaroslav; Abadias, M.; Pavlík, Ivan; Schraml, Peter; Broďák, Miloš; Villoria, Jesús; Sust, Mariá

doi:10.1016/j.eururo.2009.04.045

Cited by 30 publications

(19 citation statements)

References 29 publications

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“…Preliminary findings look promising, with results similar to those for oxybutynin during a randomized trial [79]. Side effects include nausea, headache, and vertigo [79].…”

Section: Current Overactive Bladder Treatmentsmentioning

confidence: 81%

“…Cizolirtine citrate is a substance P and calcitonin gene-related peptide release modulator that is being evaluated in the treatment of OAB in humans [78,79]. Preliminary findings look promising, with results similar to those for oxybutynin during a randomized trial [79]. Side effects include nausea, headache, and vertigo [79].…”

Section: Current Overactive Bladder Treatmentsmentioning

confidence: 89%

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The Overactive Bladder: New Concepts of Etiology and Treatment

Lee

Goldman

2010

Curr Bladder Dysfunct Rep

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Overactive bladder (OAB) is a disorder characterized by urinary urgency. In the past, the pathophysiology and treatment of OAB focused on the parasympathetic efferent innervation of detrusor smooth muscle cells. However, recent evidence has provided a clearer understanding of the neurological, chemical, and functional physiology of the bladder and how it relates to the pathophysiology of OAB. Urothelial cells, sensory neurons, and interstitial cells of Cajal have secretory and receptor functions that play an important role in bladder function and dysfunction. As we learn more about bladder function and the mechanism of current OAB treatments, newer forms of therapy are emerging. These include neuromodulation, botulinum toxin, and the development of new drugs based on the pathophysiology of OAB.

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“…Preliminary findings look promising, with results similar to those for oxybutynin during a randomized trial [79]. Side effects include nausea, headache, and vertigo [79].…”

Section: Current Overactive Bladder Treatmentsmentioning

confidence: 81%

Section: Current Overactive Bladder Treatmentsmentioning

confidence: 89%

The Overactive Bladder: New Concepts of Etiology and Treatment

Lee

Goldman

2010

Curr Bladder Dysfunct Rep

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“…Cizolirtine citrate has inhibitory effect on release of calcitonin gene-related peptide and substance P. An MDRCT had comparable efficacy with cizolirtine and oxybutynin in reducing number of voids in 24 h and voided volumes in patients with overactive bladder. Dry mouth was common in oxybutynin group and gastrointestinal and neurological adverse effects were more common in cizolirtine group [68]. Phase III trial was prematurely ended in the UK and it is ongoing in Spain.…”

Section: Tachykinin Receptor Antagonistmentioning

confidence: 99%

Emerging drugs for overactive bladder

Karmarkar

Khullar

2015

Expert Opinion on Emerging Drugs

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“…A dose-finding study of patients with clinical OAB and/or urodynamic DO showed a "clear improvement" in urination frequency with orally-administered cizolirtine [22]. A phase II clinical trial showed cizolirtine to perform very similarly to the antimuscarinic oxybutynin in increasing bladder capacity and decreasing frequency of urination compared to placebo, albeit with its own side effect profile, mainly gastrointestinal effects [23]. I hope this essay has shown the breadth and diversity of current pharmacological research in treating OAB and DO.…”

Section: Cizolirtinementioning

confidence: 99%

How Drugs Modify The Micturition Reflex: A Review

Humphrey¹

2012

OPT

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Micturition -the classical term for urination -is a complex action which relies on both the lower urinary tract and the micturition areas of the central nervous system (CNS) working together. It is comprised of two phases: storage, where urine from the kidneys is stored in the bladder until it is appropriate, and voiding where the urine is expelled from the bladder via the urethra. The detrusor is the smooth muscle of the bladder which is distended upon filling and is contracted during voiding. The outlet comprises the bladder neck along with the smooth and striated urethral sphincter muscles. The outlet is contracted during filling and relaxed during voiding [1].The bladder is controlled by the CNS, both voluntarily through the somatic nervous system and also unconsciously through the two anatomical divisions of the autonomic nervous system. The sympathetic branch, when active, triggers the "fight or flight" response to danger and the parasympathetic branch allows us to relax and digest our food.Nerves from the bladder to the CNS convey bladder filling via stretch receptors in the bladder wall along with pain and temperature via receptors for noxious stimuli. Central control of micturition comes from the Pontine Micturition Centre and the Periaqueductal Gray in the Pons with higher voluntary functions located in the forebrain [2].Disorders of micturition can be categorised into storage and voiding (incontinence) symptoms. Of most interest is the storage symptom Overactive Bladder (OAB), and the diagnosis of Detrusor Overactivity (DO). The 4th International Consultation on Incontinence defines Overactive Bladder as having the storage symptoms of urgency with or without urge incontinence and is usually demonstrated by a high frequency of urination episodes per day [3]. Detrusor Overactivity is defined as involuntary detrusor contractions during the storage phase of micturition. A patient with DO will feel the need to urinate regardless of how much urine is in the bladder. DO is diagnosed through invasive testing of bladder pressure [4]. DO is not synonymous with OAB, as only 69% of male and 44% of female OAB sufferers have DO [5]. Pharmacological treatment is the first course of action for these symptoms, which can be abated theoretically by increasing bladder capacity, reducing detrusor activity and strengthening outlet sphincter resistance [2]. Therefore, a patient's micturition may be modified with drugs, hopefully to improve their quality of life.In this paper I will outline the pharmacology, efficacy and safety of the current standard drugs (antimuscarinics) for OAB and DO as well as several novel drugs where research is still ongoing, targeting both the periphery and the central nervous system, using as current data as possible. Peripheral Targets AntimuscarinicsThe parasympathetic branch of the autonomic nervous system is the main drive of bladder contraction. Nerve terminals release the transmitter chemical acetylcholine for which there are specific receptors on the detrusor muscle. Activation of these re...

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Cizolirtine Citrate Is Safe and Effective for Treating Urinary Incontinence Secondary to Overactive Bladder: A Phase 2 Proof-of-Concept Study

Cited by 30 publications

References 29 publications

The Overactive Bladder: New Concepts of Etiology and Treatment

The Overactive Bladder: New Concepts of Etiology and Treatment

Emerging drugs for overactive bladder

How Drugs Modify The Micturition Reflex: A Review

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