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Aims: To explore the role of voltage‐gated calcium channels (VGCC) in 5‐HT2A/2C receptor agonist 2,5‐dimethoxy‐4‐iodophenyl‐2‐aminopropane hydrochloride's improvement of spinal cord injury (SCI) induced detrusor sphincter dyssynergia and the expressions of the 5‐hydroxy tryptamine (5‐HT) 2A receptors and VGCCs in lumbosacral cord after SCI. Methods: Female Sprague–Dawley rats were randomized into normal control group and SCI group (N = 15 each). Cystometrogram (CMG), simultaneous CMG, and external urethral sphincter electromyography (EUS‐EMG) were conducted in all groups under urethane anesthesia. Drugs were administered intrathecally during CMG and EUS‐EMG. Rats were euthanized and L6‐S1 spinal cord were acquired for immunofluorescence. Results: In SCI rats, intrathecal administration of 2,5‐dimethoxy‐4‐iodophenyl‐2‐aminopropane hydrochloride or L‐type VGCC blocker, nifedipine, could significantly increase voiding volume, voiding efficiency, and the number of high‐frequency oscillations. They could also prolong EUS bursting activity duration on EUS‐EMG. Moreover, the effect of 2,5‐dimethoxy‐4‐iodophenyl‐2‐aminopropane hydrochloride can be eliminated with the combined administration of L‐type VGCC agonist, (±)‐Bay K 8644. No significant differences were observed in CMG after intrathecal administration of T‐type VGCC blocker TTA‐P2. Additionally, immunofluorescence of the lumbosacral cord in control and SCI rats showed that the 5‐HT2A receptor and Cav1.2 immunolabeling‐positive neurons in the anterior horn of the lumbosacral cord were increased in SCI rats. Conclusions: Our study demonstrated that 5‐HT2A/2C agonist 2,5‐dimethoxy‐4‐iodophenyl‐2‐aminopropane hydrochloride may improve SCI‐induced DSD by inhibiting the L‐type voltage‐gated calcium channel in lumbosacral cord motoneurons. [ABSTRACT FROM AUTHOR]

Objective: To examine the effects of the selective 5‐HT1A receptor agonist, NLX‐112, on urethral function in streptozotocin‐induced diabetic rats. Materials and Methods: Female Sprague–Dawley rats (n = 32) were divided into two groups: rats with type 1 diabetes mellitus (T1DM) and age‐matched normal control rats (NC). T1DM was induced by intraperitoneal injection of streptozotocin (65 mg/kg). Isovolumetric cystometry and urethral perfusion pressure (UPP) were evaluated 10 weeks postinjection in rats (n = 9 per group). The selective 5‐HT1A receptor antagonist, WAY‐100635 maleate salt, was administered after NLX‐112 hydrochloride dose–response curve was generated (intravenously). The remaining rats were used for immunofluorescence and Western blot assays. Results: Compared to controls, type 1 diabetic rats (T1D rats) had lower maximal intravesical pressure (IP max) and UPP changes. In T1D rats, NLX‐112 hydrochloride (0.003–1.0 mg/kg) induced dose‐dependent decreases in UPP nadir, IP max, high‐frequency oscillations (HFOs) rate; and increases in UPP change and HFOs amplitude. WAY‐100635 maleate salt (0.3 mg/kg) partially or completely reversed the NLX‐112‐induced changes. Immunofluorescence revealed that 5‐HT1A receptors were found in the L6‐S1 spinal cord dorsolateral nucleus, but the expression was significantly higher in the T1D rats. Additionally, Western blot showed there were significantly more 5‐HT1A receptors in the ventral L6‐S1 spinal cord of T1D rats. Conclusions: Urethral dysfunction in T1D rats was improved by NLX‐112. 5‐HT1A receptors were upregulated in the dorsolateral nucleus of L6‐S1 spinal cord in T1D rats. These findings suggest that NLX‐112 may constitute a novel therapeutic strategy to treat diabetic urethral dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: To examine the effect of intrathecal (i.t.) serotonin (5‐hydroxytryptamine) 5‐HT7 agonist administration on voiding function in the urethane‐anesthetised rat, and the change in 5‐HT7 receptor (5‐HT7R) expression in the lumbosacral cord Onuf's nucleus after spinal cord injury (SCI). Materials and methods: In all, 32 female Sprague–Dawley (SD) rats were equally divided into a spinally intact (SI) group and SCI group (n = 16 each). At 8 weeks after transection, half of the rats underwent continuous cystometry under urethane anaesthesia, and the 5‐HT7R‐selective agonist LP44 was given (i.t.). The remaining rats were used for pseudorabies (PRV) retrograde tracing, immunofluorescence, and Western Blot. Results: LP44 administered i.t. had no effect in the SI rats. In SCI rats, LP44 (1–30 μg/kg) induced significant dose‐dependent increases in micturition volume, voiding efficiency, number of high‐frequency oscillations per micturition; and decreases in residual volume, bladder capacity, peak bladder pressure, threshold pressure and non‐voiding contractions. The 5‐HT7R antagonist, SB‐269970 (10 μg/kg), partially reversed LP44‐induced changes. Using PRV retrograde tracing and immunofluorescence, 5‐HT7Rs were found in the L6–S1 spinal cord Onuf's nucleus in both SI and SCI rats, but the expression was significantly greater in the SCI rats. Western blot showed significantly more 5‐HT7Rs in the ventral L6–S1 spinal cord in SCI rats. Conclusion: A 5‐HT7R agonist, given i.t., improved voiding efficiency in urethane‐anesthetised SCI rats, and the 5‐HT7R was significantly up‐regulated in the lumbosacral cord Onuf's nucleus. If valid for humans, these findings suggest that the 5‐HT7R could be a target for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Aim: To investigate the value of repeat botulinum toxin A (BTX‐A) injections in patients with neurogenic detrusor overactivity (NDO). Methods: We searched the PubMed, EMBASE, and EBSCO databases for articles published until June 2016. Studies that reported the efficacy and safety of repeat BTX‐A injections for adult patients with NDO were eligible. The effect size for each outcome was calculated as the standardized mean difference ± standard error and 95% confidence interval, and was graded as small, >0.2; moderate, >0.5; or large, >0.8. The outcomes included maximum cystometric capacity (MCC), maximum detrusor pressure (MDP), reflex volume (RV), bladder compliance (BC), quality of life (QOL), and injection interval. Descriptive reviews were performed for urinary incontinence (UI) and adverse events (AEs). Results: Eighteen studies involving 1533 patients whose level of evidence ranged from 3 to 4 were included in this study. We noted non‐significant changes in MCC, MDP, RV, and BC between the first and last injections. Patients who had received ≤4 injections were found to have stable QOL improvements after the first and last injections, whereas patients who had received ≥5 injections were found to have a significant decrease in QOL after the last injection. No significant differences in injection intervals were noted after repeat BTX‐A injections, and the repeat injection failure rate was low. Conclusion: Our study demonstrated that repeat BTX‐A injections allow sustained improvements in patients with NDO. The rate of AEs was stable and low. However, additional high‐quality, large‐scale, and long‐term trials are necessary to establish the efficacy and safety of ≥5 repeat BTX‐A injections. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether the voiding dysfunction caused by spinal cord injury (SCI) in rats can be improved by i.v. administration of the serotonin (5‐HT)2A/2C receptor agonist 2,5‐dimethoxy‐4‐iodophenyl‐2‐aminopropanehydrochloride (DOI), and to discuss whether the mechanism can be ascribed to 5‐HT2A and 5‐HT 2C receptor upregulation in lumbosacral cord motoneurons. Materials and Methods: Female Sprague–Dawley rats were divided into two groups (SCI group vs normal control [NC] group). Under urethane anaesthesia, cystometry was performed to examine the variation in urodynamic variables before and after successive intrathecal (i.t.) administration of various doses of DOI into the lumbosacral cord. Changes in 5‐HT2A and ‐2C receptors in the lumbosacral cord were also investigated using immunohistochemical staining and Western blot analysis. Results: Compared with NC rats, the SCI rats had higher bladder capacity and post‐void residual urine volume, and lower voiding efficiency. After SCI, DOI improved voiding efficiency, probably via external urethral sphincter (EUS) activity. Immunohistochemical staining and Western blot analysis showed that 5‐HT2A and ‐2C receptors were upregulated in lumbosacral cord motoneurons. Conclusion: In rats with SCI, DOI can improve voiding efficiency; this may be attributable to 5‐HT2A and ‐2C receptor upregulation in lumbosacral cord motoneurons controlling EUS activity. [ABSTRACT FROM AUTHOR]

Objectives To examine the effects of the serotonin (5- HT) 2A/2C receptor agonist (2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride ( DOI) on micturition in rats with diabetes mellitus ( DM). Methods Female Sprague- Dawley rats ( n = 16) were divided into two groups: rats with Type 1 DM and age-matched control rats. DM was induced by i.p. injection of streptozotocin (65 mg/kg) and detailed cystometrogram ( CMG) studies were performed 8 weeks post-injection in all rats under urethane anaesthesia. The selective 5- HT2A antagonist ketanserin was administered after each DOI dose-response curve was plotted. All drugs were administered i.v. Results Compared with controls, comprehensive urodynamic studies showed that DM rats had a higher bladder capacity and post-void residual urine volume ( PVR), and a markedly lower voiding efficiency. In DM rats, DOI (0.01-0.3 mg/kg) induced significant dose-dependent increases in micturition volume and reductions in PVR, resulting in greater voiding efficiency. CMG measurements showed a dose-dependent increase in high-frequency oscillation ( HFO) activity, evidenced by an increased duration of HFOs per voiding. This correlated with the improved voiding efficiency. Ketanserin (0.1 mg/kg) partially or completely reversed the DOI-induced changes. Conclusions The HFOs observed in the present study seem to correlate with external urethral sphincter bursting activity during voiding. Bladder voiding efficiency was reduced in DM rats. The 5- HT2A receptor agonist can enhance HFO activity and improves voiding efficiency, and so may represent a new strategy to improve voiding efficiency after DM in experimental studies. [ABSTRACT FROM AUTHOR]

Aims Serotonin affects micturition in the normal rat through actions not only on ascending and descending spinal pathways and supraspinal centers but also on the lumbosacral spinal cord level. The selective 5-HT1A receptor agonist, 8-OH-DPAT((R)-(+)-8-hydroxy-2-(di-n-propylamino) tetralin), reversed detrusor-sphincter dyssynergia (DSD) in the spinal cord injury (SCI) rat. Rats with experimental diabetes mellitus (DM) have been shown to have both bladder and urethral dysfunction during reflex voiding. We therefore examined the effects of 8-OH-DPAT on micturition in DM rats. Methods Female Sprague-Dawley rats were used. DM was induced by an intraperitoneal injection of streptozotocin (STZ, 65 mg/kg) and a cystometric study was performed 8 weeks post-injection. External urethral sphincter electromyography (EUS-EMG) was also measured. The 5-HT1A antagonist WAY-100635(N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide) was administered after each 8-OH-DPAT dose-response. Results Compared to controls, DM rats had a higher bladder capacity, residual volume, and a lower voiding efficiency. In DM rats, 8-OH-DPAT (3-1,000 µg/kg, i.v.) induced significant dose-dependent increases in micturition volume, and decreases in residual volume, resulting in increases in voiding efficiency. During the micturition, there was a dose-dependent increased phasic EUS activity correlated with the improved voiding efficiency. WAY-100635 (300 µg/kg, i.v.) reversed the 8-OH-DPAT-induced changes. Conclusions Both the bladder voiding efficiency and the periodic EUS activity were decreased in DM rats. 5-HT1A receptor agonism promoted periodic EUS activity, thereby improving voiding efficiency. Whether or not these results may have implications for the future treatment of voiding dysfunction in DM patients remains to be studied. Neurourol. Urodynam. 31:168-173, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aims: To explore the role of voltage-gated calcium channels (VGCC) in 5-HT 2A/2C receptor agonist 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride's improvement of spinal cord injury (SCI) induced detrusor sphincter dyssynergia and the expressions of the 5-hydroxy tryptamine (5-HT) 2A receptors and VGCCs in lumbosacral cord after SCI., Methods: Female Sprague-Dawley rats were randomized into normal control group and SCI group (N = 15 each). Cystometrogram (CMG), simultaneous CMG, and external urethral sphincter electromyography (EUS-EMG) were conducted in all groups under urethane anesthesia. Drugs were administered intrathecally during CMG and EUS-EMG. Rats were euthanized and L6-S1 spinal cord were acquired for immunofluorescence., Results: In SCI rats, intrathecal administration of 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride or L-type VGCC blocker, nifedipine, could significantly increase voiding volume, voiding efficiency, and the number of high-frequency oscillations. They could also prolong EUS bursting activity duration on EUS-EMG. Moreover, the effect of 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride can be eliminated with the combined administration of L-type VGCC agonist, (±)-Bay K 8644. No significant differences were observed in CMG after intrathecal administration of T-type VGCC blocker TTA-P2. Additionally, immunofluorescence of the lumbosacral cord in control and SCI rats showed that the 5-HT 2A receptor and Cav1.2 immunolabeling-positive neurons in the anterior horn of the lumbosacral cord were increased in SCI rats., Conclusions: Our study demonstrated that 5-HT 2A/2C agonist 2,5-dimethoxy-4-iodophenyl-2-aminopropane hydrochloride may improve SCI-induced DSD by inhibiting the L-type voltage-gated calcium channel in lumbosacral cord motoneurons., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)