Effects of Distigmine on Electrical Field Stimulation-Induced Contraction of Mouse Urinary Bladder Smooth Muscles

Obara, Kazuo; Kobayashi, Yurina; Chino, Daisuke; Tanaka, Yoshio

doi:10.1159/000452222

Cited by 6 publications

(4 citation statements)

References 25 publications

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“…However, looking at the urodynamic reports in MG (Table 3 ) and neuro-urology reports [ 8 , 9 ], there might be a direct cause and/or a secondary or associated cause producing LUTS in MG. Detrusor overactivity (DO; as seen in Table 1 ) is usually attributed to the brain/supra-sacral spinal cord lesions, but it might also originate from partial peripheral nerve lesion (by irritation and ephaptic transmission of the nerve fibers). Another possibility for DO is that pyridostigmine, commonly prescribed to ameliorate muscular weakness in MG, stimulates bladder smooth muscles enough to generate DO [ 12 ]. In our previous study [ 13 ], a 42-year-old man with MG (MGFA2, under 120 mg/day pyridostigmine) showed DO and small bladder capacity (150 mL) on urodynamics.…”

Section: Discussionmentioning

confidence: 99%

Lower Urinary Tract Symptoms in Myasthenia Gravis

2021

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It remains uncertain to what extent lower urinary tract (LUT) symptom (LUTS) is a comorbidity of myasthenia gravis (MG). We prospectively administered a LUTS questionnaire devised for detecting neurogenic pelvic organ dysfunction (not validated) in an MG group and a healthy control group and compared the results. The MG group comprised 21 patients: 15 women and 6 men, with age range 22–73 (mean 47) years, illness duration range 0.2–8 (mean 3.5) years, median Myasthenia Gravis Foundation of America (MGFA) grade 2, all walking independently. Therapies included thymectomy in 17, predonisolone 5–20 mg/day in 10, and pyridostigmine bromide 60–180 mg/day in 9 patients. The control group, who were undergoing an annual health survey, comprised 235 consecutive subjects: 120 women and 115 men, with age range 30–69 (mean 48) years. The questionnaire had 9 questions. Each question was scored from 0 (none) to 3 (severe) with an additional quality of life (QOL) index scored from 0 (satisfied) to 3 (extremely dissatisfied). Statistical analysis was made using Student’s t test. Compared with the control subjects, the frequency of LUTSs in the MG patients was significantly higher for daytime frequency (43%; p < 0.01), nocturia (24%; p < 0.01), and urinary incontinence (43%; p < 0.05). The LUTS-related QOL index for the MG patients was significantly higher for MG patients as a whole than that for all control patients (29%) (p < 0.05). In conclusion, our study results showed that MG patients had significantly more LUTSs (overactive bladder) than healthy control subjects and had worse LUTS-related QOL; therefore, amelioration of LUTS in MG is important.

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Section: Discussionmentioning

confidence: 99%

Lower Urinary Tract Symptoms in Myasthenia Gravis

2021

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“…Therefore, these contractions were caused by both ACh (the atropine-sensitive component) and ATP (the α,β-mATP-sensitive component). 44) To confirm that distigmine augments the ACh-induced contractile component, we examined its effects on contraction generated in the presence of α,β-mATP (10 −4 M). Distigmine (10 −6 M) substantially enhanced the contractile component and subsequent atropine (10 −6 M) administration almost completely suppressed it (Fig.…”

Section: Effects Of Distigmine On Ubsm Contrac-tile Responses Elicitementioning

confidence: 99%

“…Therefore, distigmine clearly augmented the ACh-mediated contractile component. 44) We also examined the effects of distigmine on the EFSinduced contractile component generated in the presence of atropine to verify that distigmine does not influence ATPinduced contraction. Distigmine (10 −6 M) did not significantly affect the contractile component generated in the presence of atropine (10 −6 M) (p >0.05 for atropine (10 −6 M) vs. atropine (10 −6 M) + distigmine (10 −6 M)).…”

Section: Effects Of Distigmine On Ubsm Contrac-tile Responses Elicitementioning

confidence: 99%

Effects of Distigmine on the Mechanical Activity of Urinary Bladder Smooth Muscle

Obara

Tanaka

2019

Biological & Pharmaceutical Bulletin

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Distigmine bromide (distigmine) is a reversible carbamate cholinesterase (ChE) inhibitor. Its principle clinical application is in the treatment of myasthenia gravis. Distigmine is also used as a remedy for dysuria and glaucoma. Its effectiveness in the management of dysuria has been demonstrated in several clinical reports. Distigmine may improve (enhance) urinary bladder smooth muscle (UBSM) contraction during micturition by inhibiting acetylcholine (ACh) decomposition. However, the pharmacological effects of distigmine on UBSM have not been adequately studied so far. In this review article, we summarize the reported effects of distigmine on the contractile responses elicited by exogenous and endogenous ACh in isolated UBSM preparations. We also discuss the effects of distigmine on the UBSM basal tone and the contractile response of UBSM to ATP, which is co-released with ACh from parasympathetic nerve terminals.

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“…Therefore, our laboratory started pharmacological studies on the effects of distigmine on urinary bladder (UB) motility and has previously reported results supporting the clinical effectiveness and usefulness of distigmine. [10][11][12][13][14][15][16][17][18] The most remarkable pharmacological characteristic of distigmine was the persistence of its effect. In particular, distigmine was found to potentiate the UB internal pressure via the micturition reflex for more than 12 h. 17) Interestingly, the long-lasting potentiating effect of distigmine on intravesical pressure persisted even after distigmine disappeared from the blood.…”

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confidence: 99%

Long-Lasting Inhibitory Effects of Distigmine on Recombinant Human Acetylcholinesterase Activity

Obara

Chino

Tanaka

2017

Biological & Pharmaceutical Bulletin

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To elucidate the mechanism whereby distigmine, an underactive bladder remedy, potentiates urinary bladder contractions long-lastingly, the inhibition of recombinant human acetylcholinesterase (rhAChE) by distigmine was investigated. A centrifugal ultrafiltration device, Nanosep ® 10K, was used to separate rhAChE and a bound inhibitor from an unbound inhibitor, reaction substrate, and reaction product. This allowed the same aliquot of rhAChE to be repeatedly assayed for up to 48 h to confirm the long-lasting binding of an inhibitor. Cholinesterase (ChE) inhibitors, distigmine, pyridostigmine, neostigmine, and ambenonium, were tested. The dissociation rate constant (k diss ) and dissociation half-life (t 1/2 ) of each inhibitor were determined based on the changes in rhAChE activity. Within 2-4 h after removing pyridostigmine, neostigmine, or ambenonium, the rhAChE activity was restored to the control levels. The k diss values for pyridostigmine, neostigmine, and ambenonium were calculated to be 0.51 0.05, 0.66 0.03, and 1.41 0.08 h 1 , and the t 1/2 values were calculated to be 1.36, 1.05, and 0.49 h, respectively. With distigmine, the rhAChE activity initially dropped to 17% of that in the control and then slowly recovered to only 50% by 48 h after drug removal. The k diss and t 1/2 values of distigmine were calculated to be 0.012 0.001 h 1 and 57.8 h, respectively. Based on the t 1/2 values, distigmine was judged to dissociate from acetylcholinesterase (AChE) 40-120-fold slower than the other ChE inhibitors did. This may explain the long-lasting potentiation of urinary bladder contractions and motility by distigmine as a treatment for an underactive bladder. Key words distigmine bromide; acetylcholinesterase; cholinesterase inhibitorDistigmine is a reversible cholinesterase (ChE) inhibitor from the class of carbamates. It was chemically synthesized by Schmid 1) and has a chemical structure consisting of two molecules of pyridostigmine connected by hexamethylene bonds (Fig. 1). Distigmine is used clinically in some Asian and European countries, including Japan and Germany, 2-8) and the main clinical indication for distigmine is myasthenia gravis.2,9) However, in Japan, distigmine has also been used for glaucoma 3) and an underactive bladder. 4-8)The effectiveness and usefulness of distigmine for underactive bladder treatment have been shown in many clinical studies. [4][5][6][7][8] However, the experimental evidence to support these clinical reports was not convincing. Therefore, our laboratory started pharmacological studies on the effects of distigmine on urinary bladder (UB) motility and has previously reported results supporting the clinical effectiveness and usefulness of distigmine. [10][11][12][13][14][15][16][17][18] The most remarkable pharmacological characteristic of distigmine was the persistence of its effect. In particular, distigmine was found to potentiate the UB internal pressure via the micturition reflex for more than 12 h. 17)Interestingly, the long-lasting potentiating effect of distigmine o...

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Effects of Distigmine on Electrical Field Stimulation-Induced Contraction of Mouse Urinary Bladder Smooth Muscles

Cited by 6 publications

References 25 publications

Lower Urinary Tract Symptoms in Myasthenia Gravis

Lower Urinary Tract Symptoms in Myasthenia Gravis

Effects of Distigmine on the Mechanical Activity of Urinary Bladder Smooth Muscle

Long-Lasting Inhibitory Effects of Distigmine on Recombinant Human Acetylcholinesterase Activity

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