Log in to MyKarger to check if you already have access to this content.

Buy FullText & PDF Unlimited re-access via MyKarger Unrestricted printing, no saving restrictions for personal use read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.

Save over 20% compared to the individual article price.

Learn more

Access via DeepDyve Unlimited fulltext viewing of this article Organize, annotate And mark up articles Printing And downloading restrictions apply

Select

Subscribe Access to all articles of the subscribed year(s) guaranteed for 5 years Unlimited re-access via Subscriber Login or MyKarger Unrestricted printing, no saving restrictions for personal use read more

Subcription rates

Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview

Received: October 06, 2022
Accepted: November 27, 2022
Published online: December 19, 2022

Number of Print Pages: 6
Number of Figures: 1
Number of Tables: 2

ISSN: 0378-7346 (Print)
eISSN: 1423-002X (Online)

For additional information: https://www.karger.com/GOI

Abstract

Objectives: Nocturia was commonly treated with drugs burdened with high costs and numerous side effects; in fact, more than 70% of patients drop out of long-term treatment. Protopine and nuciferine are two alkaloids that have different effects on the neurotransmitter receptors involved in the regulation mechanism of the onset of urinary stimuli. The aim of the study was to evaluate the efficacy in controlling primarily nocturia and secondarily urgency and dysuria after 3 months of treatment with combination therapy of protopine and nuciferine syrup. Design: This is a prospective cohort study in which all patients were diagnosed with overactive bladder syndrome (OAB) and the presence of the following symptoms: nocturia, urgency, and dysuria. Thirty patients were administered 10 mL/die (16.6 mg of nuciferine, 0.09 mg of protopine) of syrup for 3 months. Patients were evaluated at baseline (T0) with the International Consultation on Incontinence Questionnaire (ICIQ), Visual Analogue Scale (VAS) for the evaluation of dysuria, Patient Perception of Intensity of Urgency Scale (PPIUS) and at 3 months (T1) with the Patients’ Global Impression of Change (PGI-C) scale, PPIUS, VAS, and ICIQ. Participants: Women with diagnosis of OAB; the presence of nocturia, urgency, and dysuria symptoms agreeing to undergo treatment and compiling informed consent; and the absence of contraindications to the use of active ingredients were included in the study. Setting: Patients were recruited at T0 during the visit to the Uro-Gynecology clinic of the University of “Campus Bio-Medico” and visited again 3 months (T1) after the initiation of therapy. Methods: We explored survey data by descriptive statistics: in particular, continuous values (i.e., ICIQ) have been summarized by mean and standard deviation of discrete ordinal values (i.e., VAS, PPIUS, and bladder diary parameters at T0 and T1) by median, minimum, and maximum reported scores. Where we could assume normality in distribution, assessed by the Shapiro-Wilk test and the evaluation of the QQ plot, we compared the observation of T0 and T1 with the paired Student’s t test; otherwise, we tested differences in distribution with the paired Mann-Whitney U test. Results: Thirty patients completed a 3-month therapy. The ICIQ and VAS questionnaires for the assessment of dysuria, both, reported an improvement in dysuria at T1 (p < 0.001). The PPIUS questionnaire reported an improvement in urinary urgency at T1 (p < 0.001). The PGI-C scale in T1 indicated an improvement in symptoms: 93% for nocturia, 70% for urinary urgency, and 63% for dysuria. Limitations: The weaknesses of this study are the small number of patients; as a pilot study, the study design was not randomized with a placebo and without blinding; and the short follow-up. Conclusions: Protopine and nuciferine can be an interesting alternative to primarily treat and reduce nocturia episodes, in addition to improving OAB-related urgency and dysuria.

© 2022 S. Karger AG, Basel

References Pauwaert K, Goessaert AS, Ghijselings L, Bower W, Depypere H, Everaert K. Characterizing nocturia among Belgian healthy postmenopausal women: prevalence, degree of bother, etiology and risk factors for nocturia. Maturitas. 2021;143:41–6. Ancoli-Israel S, Bliwise DL, Nørgaard JP. The effect of nocturia on sleep. Sleep Med Rev. 2011;15(2):91–7. Kelleher C, Hakimi Z, Zur R, Siddiqui E, Maman K, Aballea S, et al. Efficacy and tolerability of mirabegron compared with antimuscarinic monotherapy or combination therapies for overactive bladder: a systematic review and network meta-analysis. Eur Urol. 2018;74(3):324–33. Yeaw J, Benner JS, Walt JG, Sian S, Smith DB. Comparing adherence and persistence across 6 chronic medication classes. J Manag Care Pharm. 2009;15(9):728–40. Fogaing C, Mossa AH, Campeau L. Are beta 3 adrenergic agonists now the preferred pharmacologic management of overactive bladder? Curr Urol Rep. 2020;21(12):49. Chiancone F, Carrino M, Fedelini M, Fabiano M, Persico F, Meccariello C, et al. The role of protopine associated with Nuciferine in controlling adverse events during hyperthermic intravesical chemotherapy instillations. A nutraceutical approach to control adverse event during intravesical instillations. Arch Ital Urol Androl. 2020;92(3). Xu LF, Chu WJ, Qing XY, Li S, Wang XS, Qing GW, et al. Protopine inhibits serotonin transporter and noradrenaline transporter and has the antidepressant-like effect in mice models. Neuropharmacology. 2006;50(8):934–40. Araklitis G, Robinson D, Cardozo L. Cognitive effects of anticholinergic load in women with overactive bladder. Clin Interv Aging. 2020;15:1493–503. Nitz NM, Jumadilova Z, Darkow T, Frytak JR, Bavendam T. Medical costs after initiation of drug treatment for overactive bladder: effects of selection bias on cost estimates. Am J Manag Care. 2005;11(4 Suppl):S130–9. Gözen AS, Umari P, Scheitlin W, Su FE, Akin Y, Rassweiler J. Effectivity of intravescical thermo-chemotherapy prophylaxis for patients with high recurrence and progression risk for non-muscle invasive bladder cancer. Arch Ital Urol Androl. 2017; 89(2), 102–5. Kardos J, Blaskó G, Simonyi M. Enhancement of gamma aminobutyric acid receptor binding by protopine type alkaloids. Arzneimittelforschung. 1986;36(6):939–40. Fedurco M, Gregorová J, Šebrlová K, Kantorová J, Peš O, Baur R, et al. Modulatory effects of eschscholzia californica alkaloids on recombinant GABA A receptors. Biochem Res Int. 2015;2015:617620. Häberlein H, Tschiersch KP, Boonen G, Hiller KO. Chelidonium majus L.: components with in vitro affinity for the GABAA receptor. Positive cooperation of alkaloids. Planta Med. 1996;62(3) 227–31. Usiello A, Baik JH, Rougé-Pont F, Picetti R, Dierich A, LeMeur M, et al. Distinct functions of the two isoforms of dopamine D2 receptors. Nature. 2000;408(6809):199–203. Kim YT, Kwon DD, Kim J, Kim DK, Lee JY, Chancellor MB. Gabapentin for overactive bladder and nocturia after anticholinergic failure. Int Braz J Urol. 2004;30(4):275–8. Chua ME, See MC 4th, Esmeňa EB, Balingit JC, Morales ML Jr. Efficacy and safety of gabapentin in comparison to solifenacin succinate in adult overactive bladder treatment. Low Urin Tract Symptoms. 2018;10(2):135–42. Yoshimura N, Kuno S, Chancellor MB, De Groat WC, Seki S. Dopaminergic mechanisms underlying bladder hyperactivity in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway. Br J Pharmacol. 2003;139(8):1425–32. Ustünes L, Laekeman GM, Gözler B, Vlietinck AJ, Ozer A, Herman AG. In vitro study of the anticholinergic and antihistaminic activities of Protopine and some derivatives. J Nat Prod. 1988; 51(5):1021–2. Farrell MS, McCorvy JD, Huang XP, Urban DJ, White KL, Giguere PM, et al. In vitro and in vivo characterization of the alkaloid nuciferine. PLoS One. 2016;11(3):e0150602. Zhang C, Deng J, Liu D, Tuo X, Yu Y, Yang H, et al. Nuciferine inhibits proinflammatory cytokines via the PPARs in LPS-induced RAW264.7 cells. Molecules. 2018;23(10), 2723. Pelletier EM, Vats V, Clemens JQ. Pharmacotherapy adherence and costs versus nonpharmacologic management in overactive bladder. Am J Manag Care. 2009;15(4 Suppl), S108–S114. Hiller KO, Ghorbani M, Schilcher H. Antispasmodic and relaxant activity of chelidonine, protopine, coptisine, and Chelidonium majus extracts on isolated Guinea-pig ileum. Planta Med. 1998;64(8):758–60. Zhang L, Gao J, Tang P, Chong L, Liu Y, Liu P, et al. Nuciferine inhibits LPS-induced inflammatory response in BV2 cells by activating PPAR-γ. Int Immunopharmacol. 2018;63:9–13. Bae D-S, Kim Y-H, Pan C-H, Nho C-W, Samdan J, Yansan J, et al. Protopine reduces the inflammatory activity of lipopolysaccharide-stimulated murine macrophages. BMB Rep. 2012;45(2):108–13. Pesonen JS, Cartwright R, Vernooij RWM, Aoki Y, Agarwal A, Mangera A, et al. The impact of nocturia on mortality: a systematic review and meta-analysis. J Urol. 2020;203(3):486–95. Article / Publication Details

First-Page Preview

Received: October 06, 2022
Accepted: November 27, 2022
Published online: December 19, 2022

Number of Print Pages: 6
Number of Figures: 1
Number of Tables: 2

ISSN: 0378-7346 (Print)
eISSN: 1423-002X (Online)

For additional information: https://www.karger.com/GOI