Clinical efficacy of distigmine bromide in the treatment of patients with underactive detrusor

Bougas, D; Mitsogiannis, Iraklis; Mitropoulos, Dionisios; Kollaitis, G.; Serafetinides, Efrem N.; Giannopoulos, Aris

doi:10.1007/s11255-004-0847-8

Cited by 37 publications

(24 citation statements)

References 11 publications

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“…The use of available oral drugs show limited clinical benefits,10, 11 and have numerous undesired side effects 12. Willing and physically able patients can use intermittent self‐catheterization.…”

Section: Introductionmentioning

confidence: 99%

A 3D Printed Implantable Device for Voiding the Bladder Using Shape Memory Alloy (SMA) Actuators

et al. 2017

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Underactive bladder or detrusor underactivity (DU) is defined as a reduction of contraction strength or duration of the bladder wall. Despite the serious healthcare implications of DU, there are limited solutions for affected individuals. A flexible 3D printed implantable device driven by shape memory alloys (SMA) actuators is presented here for the first time to physically contract the bladder to restore voluntary control of the bladder for individuals suffering from DU. This approach is used initially in benchtop experiments with a rubber balloon acting as a model for the rat bladder to verify its potential for voiding, and that the operating temperatures are safe for the eventual implantation of the device in a rat. The device is then implanted and tested on an anesthetized rat, and a voiding volume of more than 8% is successfully achieved for the SMA‐based device without any surgical intervention or drug injection to relax the external sphincter.

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Section: Introductionmentioning

confidence: 99%

A 3D Printed Implantable Device for Voiding the Bladder Using Shape Memory Alloy (SMA) Actuators

et al. 2017

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confidence: 99%

“…In particular, distigmine is one of the most important clinical urology therapeutics employed to treat lower urinary tract dysfunction and this compound is used for neurogenic underactive bladder ascribed to surgery, spinal cord injury, and diabetes. [2][3][4][5][6][7][8] It is also effective against drug-and prostate enlargement-induced dysfunctions of urinary excretion. [9][10][11][12][13] Distigmine thus plays a significant role as a principal therapeutic for urinary excretion dysfunctions associated with an underactive bladder, whereas new generations of anticholinergic drugs or beta3 adrenoceptor agonists tend to be employed to treat conditions associated with an overactive bladder.…”

mentioning

confidence: 99%

Distigmine Bromide Produces Sustained Potentiation of Guinea-Pig Urinary Bladder Motility by Inhibiting Cholinesterase Activity

Obara

Chino

Tanaka

2017

Biological & Pharmaceutical Bulletin

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Distigmine is a cholinesterase (ChE) inhibitor used for the treatment of detrusor underactivity in Japan. Distigmine's pharmacological effects are known to be long-lasting, but the duration of its effect on urinary bladder contractile function has not been fully elucidated. The present study aimed to determine these effects in relation to the plasma concentrations of distigmine and its inhibition of ChE activities in blood, plasma, and bladder tissue. Intravesical pressures were recorded in anesthetized guinea-pigs for 12 h after the intravenous administration of saline or distigmine (0.01-0.1 mg/kg). Plasma distigmine concentrations were measured by liquid chromatograph-tandem mass spectrometry (LC-MS/MS), while ChE activities were assayed using 5,5′-dithiobis(2-nitrobenzoic acid). Distigmine (0.1 mg/kg) significantly increased the maximum intravesical pressure at micturition reflex for 12 h post-administration. In contrast, plasma distigmine was only detectable for 6 h post-administration in these animals and a one-compartment model calculated an elimination half-life of 0.7 h. However, bladder and blood acetylcholinesterase activities were significantly inhibited for 12 h after distigmine administration, although plasma ChE activities were not affected. The pharmacodynamic effects of distigmine thus persisted after its elimination from the circulation, indicating that it may bind to bladder acetylcholinesterase, producing sustained enzyme inhibition and enhancement of bladder contractility.Key words distigmine bromide; acetylcholinesterase; guinea-pig urinary bladder; pharmacokinetics; cystometry; intravesical pressure Distigmine bromide (distigmine) is a synthetic reversible cholinesterase (ChE) inhibitor. Its chemical structure consists of two molecules of pyridostigmine, connected by a hexamethylene structure. Clinically, this ChE inhibitor is principally used to treat Myasthenia gravis.1) In addition, glaucoma and underactive bladder are common indications for distigmine therapy in Japan. In particular, distigmine is one of the most important clinical urology therapeutics employed to treat lower urinary tract dysfunction and this compound is used for neurogenic underactive bladder ascribed to surgery, spinal cord injury, and diabetes. [2][3][4][5][6][7][8] It is also effective against drug-and prostate enlargement-induced dysfunctions of urinary excretion.9-13) Distigmine thus plays a significant role as a principal therapeutic for urinary excretion dysfunctions associated with an underactive bladder, whereas new generations of anticholinergic drugs or beta3 adrenoceptor agonists tend to be employed to treat conditions associated with an overactive bladder.Although a relatively large number of clinical reports have indicated the significant therapeutic efficacy of distigmine in urine storage disorders, there is a limited experimental evidence base relevant to its use in these conditions. In response to this, we have started to investigate the pharmacological effects of distigmine on urinary bladder contra...

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“…1), a reversible and long-acting carbamate cholinesterase inhibitor, has been clinically used to treat patients with voiding dysfunction associated with impaired detrusor contractility. 9-11) Bougas et al 9) reported that treatment with distigmine resulted in a statistically significant reduction in residual volume and percentage residual volume, obviating the need for intermittent selfcatheterization in patients with detrusor underactivity. In addition, the maximum flow rate and detrusor pressure at maximum flow increased.…”

mentioning

confidence: 99%

Demonstration of Muscarinic and Nicotinic Receptor Binding Activities of Distigmine to Treat Detrusor Underactivity

Harada

Fushimi

Kato

et al. 2010

Biological & Pharmaceutical Bulletin

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Impaired bladder emptying can be caused by chronic conditions such as bladder outlet obstruction in men with benign prostatic hyperplasia and impaired detrusor contractility in patients of either sex. 1) Detrusor underactivity is defined as a contraction of reduced strength and/or duration resulting in prolonged bladder emptying within a normal time span. 2) Some of the established causes of detrusor underactivity include neurogenic, myogenic, aging, and medication side effects.3) The medical treatment for detrusor underactivity aims to enhance detrusor contractility and to reduce urethral outlet resistance thereby improving voiding. Standard pharmacotherapy includes the use of a-adrenoceptor antagonists to reduce outlet resistance, muscarinic agonists, and acetylcholinesterase (AChE) inhibitors.Pharmacotherapy using cholinomimetic drugs such as muscarinic agonists and AChE inhibitors has been used to treat impaired bladder emptying 4,5) since these drugs improve detrusor contractility by activating the parasympathetic cholinergic system. AChE inhibitors are considered to increase detrusor contractility by inactivating cholinesterase, thus maintaining cholinergic stimulation. Alternatively, the potential interaction of AChE inhibitors with cholinergic receptors has been also implicated in the therapeutic and/or side-effects associated with this class of compounds. 6,7) It was previously shown that neostigmine interacts directly with muscarinic and nicotinic receptor sites. [6][7][8] Distigmine bromide (distigmine) (Fig. 1), a reversible and long-acting carbamate cholinesterase inhibitor, has been clinically used to treat patients with voiding dysfunction associated with impaired detrusor contractility. 9-11) Bougas et al. 9) reported that treatment with distigmine resulted in a statistically significant reduction in residual volume and percentage residual volume, obviating the need for intermittent selfcatheterization in patients with detrusor underactivity. In addition, the maximum flow rate and detrusor pressure at maximum flow increased. These results suggested that distigmine has clinical efficacy in patients with detrusor underactivity. 9) Horinouchi et al. 12) revealed that distigmine significantly potentiated acetylcholine (ACh)-induced contractions of the The present study was undertaken to examine whether distigmine, a therapeutic agent used to treat detrusor underactivity, binds directly to muscarinic and nicotinic receptors. We used radioreceptor binding assays and compared the effects of distigmine with those of neostigmine and donepedil. The inhibitory effect of distigmine on the blood acetylcholinesterase (AChE) activity was significantly weaker than that of neostigmine.

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Clinical efficacy of distigmine bromide in the treatment of patients with underactive detrusor

Abstract: Distigmine bromide shows clinical efficacy in patients with poor detrusor function and may therefore be used alternatively in selected cases.

Cited by 37 publications

References 11 publications

A 3D Printed Implantable Device for Voiding the Bladder Using Shape Memory Alloy (SMA) Actuators

A 3D Printed Implantable Device for Voiding the Bladder Using Shape Memory Alloy (SMA) Actuators

Distigmine Bromide Produces Sustained Potentiation of Guinea-Pig Urinary Bladder Motility by Inhibiting Cholinesterase Activity

Demonstration of Muscarinic and Nicotinic Receptor Binding Activities of Distigmine to Treat Detrusor Underactivity

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