What do we know about duloxetine's mode of action? Evidence from animals to humans

BJOG : an International Journal of Obstetrics and Gynaecology
B Schuessler

Abstract

The serotonin (5-hydroxytryptamine [5-HT]) and noradrenalin (NA) reuptake inhibitor duloxetine is currently the only widely approved pharmacological treatment option for women with stress urinary incontinence (SUI). The rationale for employing duloxetine in SUI is based on the role of 5-HT and NA in the neurological control of the lower urinary tract. Animal studies have shown that duloxetine increases the concentration of 5-HT and NA in the sacral spinal cord, thereby facilitating an increased activity of the external urethral sphincter (rhabdosphincter) and preventing urine leakage during the storage phase of the micturition cycle. Importantly, 5-HT and NA exert only a modulatory effect as they are not able to directly excite motor neurons. Glutamate is the key descending neurotransmitter and can be considered as the "on/off" switch for micturition. In the absence of glutamate, no rhabdosphincter activity is observed, irrespective of the presence of 5-HT and NA. Hence, duloxetine enhances sphincter activity during urine storage when glutamate is released but allows complete relaxation of the rhabdosphincter once glutamate release is inhibited during the voiding phase. The efficacy of duloxetine for treating women with SUI, as...Continue Reading

References

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Citations

Nov 5, 2013·Progrès en urologie : journal de l'Association française d'urologie et de la Société française d'urologie·X GameG Karsenty
Aug 5, 2008·Clinical Obstetrics and Gynecology·Stanley J Birge
Apr 1, 2010·Therapeutic Advances in Endocrinology and Metabolism·Mitra TavakoliRayaz A Malik
Sep 17, 2014·Nature Reviews. Urology·Qi-Xiang SongMargot S Damaser
May 27, 2011·Women's Health·Christel Renoux, Samy Suissa
Mar 27, 2015·PloS One·Marco RedaelliCarla Mucignat-Caretta
Aug 18, 2016·Nature Reviews. Urology·Israel Franco
Dec 20, 2013·International Journal of Environmental Research and Public Health·Xinyan Zhao, Tao Dong
Jul 17, 2007·The Journal of Urology·Israel Franco
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Mar 13, 2012·International Journal of Urology : Official Journal of the Japanese Urological Association·Naoki Yoshimura, Minoru Miyazato
Apr 13, 2012·Genome Medicine·Yvonne Y Li, Steven Jm Jones
Jan 6, 2011·Current Neurology and Neuroscience Reports·Lynne T ShusterPetra M Casey
May 16, 2019·Clinical Neuropharmacology·Na Young KimYong Wook Kim
Jan 5, 2014·The Cochrane Database of Systematic Reviews·Michael P T LunnPhilip J Wiffen
Jun 15, 2007·Current Opinion in Urology

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