Local-anesthetic like inhibition of the cardiac sodium channel Nav1.5 α-subunit by 5-HT 3 receptor antagonists

Klooster, Mariet P. van't; Foadi, Nilufar; Hage, Axel; Stoetzer, Carsten; Wegner, Florian; Eberhardt, Mirjam; Leffler, Andreas

doi:10.1016/j.ejphar.2016.07.020

Cited by 4 publications

(3 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it has been hypothesized that 5-Hydrotryptamine-3 (5HT3) receptor antagonists block cardiac sodium channels, widening the QT interval. This hypothesis was investigated in the study conducted by Klooster et al [ 32 ]. Effects of 5-Hydrotryptamine-3 (5HT3) receptor antagonists on human α-subunit Nav1.5 (cardiac sodium channel) heterologously expressed in HEK293 cells were assessed, and it was demonstrated that all 5-Hydrotryptamine-3 (5HT3) receptor antagonists including ondansetron inhibit Nav1.5 in a concentration and state-dependent manner [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Ondansetron-induced QT prolongation among various age groups: a systematic review and meta-analysis

et al. 2023

View full text Add to dashboard Cite

Background Ondansetron is a selective 5-hydroxytryptamine type 3 serotonin-receptor antagonist with antiemetic properties used inadvertently in the emergency department for controlling nausea. However, ondansetron is linked with a number of adverse effects, including prolongation of the QT interval. Therefore, the purpose of this meta-analysis was to assess the occurrence of QT prolongation in pediatric, adult, and elderly patients receiving oral or intravenously administered ondansetron. Methods A thorough electronic search was conducted on PubMed (Medline) and Cochrane Library from the databases' inception to August 10, 2022. Only those studies were considered in which ondansetron was administered orally or intravenously to participants for the treatment of nausea and vomiting. The prevalence of QT prolongation in multiple predefined age groups was the outcome variable. Analyses were conducted using Review manager 5.4 (Cochrane collaboration, 2020). Results A total of 10 studies involving 687 ondansetron group participants were statistically analyzed. The administration of ondansetron was associated with a statistically significant prevalence of QT prolongation in all age groups. An age-wise subgroup analysis was conducted which revealed that the prevalence of QT prolongation among participants younger than 18 years was not statistically significant, whereas it was statistically significant among participants aged 18–50 years and among patients older than 50 years. Conclusions The present meta-analysis provides further evidence that oral or intravenous administration of Ondansetron may lead to QT prolongation, particularly among patients older than 18 years of age.

show abstract

Section: Discussionmentioning

confidence: 99%

Ondansetron-induced QT prolongation among various age groups: a systematic review and meta-analysis

et al. 2023

View full text Add to dashboard Cite

show abstract

“…One way to investigate if granisetron produce local anestheticlike effects in humans could be to record changes in skin sensitivity to mechanical stimuli (Aβ-fibers), heat stimuli (Cfibers), and cold stimuli (Aδ-fibers) after injection of the substance (16,(27)(28)(29)(30)(31)(32). Hence, this study aimed to investigate the effect by granisetron on facial skin-sensitivity and comparing it to the effect of lidocaine and isotonic saline.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Granisetron on Sensory Detection and Pain Thresholds in Facial Skin of Healthy Young Males

et al. 2020

View full text Add to dashboard Cite

Background: The specific serotonin type 3 (5-HT 3 )-receptor antagonist granisetron effectively reduces clinical as well as experimental muscle pain and hyperalgesia and with a duration that exceeds that of lidocaine. Hence, it may be an alternative to lidocaine as a local anesthetic. There are also some indications that granisetron in addition to 5-HT 3 receptors blocks sodium channels. Thus, the local anesthetic effect by granisetron may resemble that of lidocaine, but this has not been tested. The aim of this study was therefore to compare the effect granisetron has on facial skin sensitivity to the effect of lidocaine and isotonic saline.Methods: This was a randomized, controlled, and double-blind study, in which 1 ml of either granisetron (test-substance), lidocaine (positive control), or isotonic saline (negative control) was injected into the skin over the masseter muscle at three different occasions in 18 healthy males (27.2 ± 5.8 years old). Skin detection thresholds and pain thresholds for thermal stimuli as well as mechanical detection thresholds and sensitivity to a painful mechanical (pinprick) stimulus were assessed before (baseline) and 5, 20, 40, and 60 min after injection. The quality and area of subjective sensory change over the cheek were assessed 20 min after injection.Results: All substances increased the mechanical detection threshold (granisetron: p = 0.011; lidocaine: p = 0.016; saline: p = 0.031). Both granisetron and lidocaine, but not isotonic saline, increased the heat detection thresholds (p < 0.001 and p < 0.02, respectively), but not the cold detection thresholds. Granisetron and lidocaine also reduced pinprick pain (p = 0.001 for each comparison). There were no significant differences between granisetron and lidocaine for any of these variables. There was no effect on thermal pain thresholds for any substance. Conclusion:The similar analgesic patterns on mechanical sensory and pain thresholds as well as thermal sensory thresholds over the facial skin by subcutaneous injection of granisetron and lidocaine shown in this study and the absence of paresthesia, in combination with the reduced pain intensity and pressure pain sensitivity shown in previous studies, indicate that granisetron might be a novel candidate as a local anesthetic.

show abstract

“…Na v 1.5 is encoded for by the gene SCN5A. This interaction causes the channel to become blocked, with tropisetron having a greater effect than ondansetron [85,86]. Ondansetron has also been found to be capable of blocking cardiac potassium channels with an increased affinity for these channels over sodium channels [85].…”

Section: Pharmacodynamicsmentioning

confidence: 99%

PharmGKB summary

Huddart

Altman

Klein

2019

Pharmacogenetics and Genomics

View full text Add to dashboard Cite

Local-anesthetic like inhibition of the cardiac sodium channel Nav1.5 α-subunit by 5-HT 3 receptor antagonists

Cited by 4 publications

References 28 publications

Ondansetron-induced QT prolongation among various age groups: a systematic review and meta-analysis

Ondansetron-induced QT prolongation among various age groups: a systematic review and meta-analysis

The Effect of Granisetron on Sensory Detection and Pain Thresholds in Facial Skin of Healthy Young Males

PharmGKB summary

Contact Info

Product

Resources

About