Background: Stimulation of 5-HT(4) receptors increases atrial chronotropic and inotropic responses. Whether other electrophysiological effects are produced is unknown. In humans and swine, 5-HT(4) receptors are present only in atrium. Therefore, the effects of a novel 5-HT(4) receptor antagonist, RS-100302, and the partial agonist cisapride on atrial flutter and fibrillation induced in swine were studied to delineate the role of the 5-HT(4) receptor in modulating atrial electrophysiological properties and the antiarrhythmic potential of RS-100302.
Methods And Results: In 17 anesthetized, open-chest, juvenile pigs, atrial flutter or fibrillation was induced by rapid right atrial pacing with or without a right atrial free wall crush injury, respectively. Atrial effective refractory period (ERP), conduction velocity, wavelength, and dispersion of refractoriness were determined during programmed stimulation via a 56-electrode mapping plaque sutured to the right atrial free wall. Ventricular electrophysiological parameters were also measured. All electrophysiological parameters were measured at baseline and after infusion of RS-100302 and cisapride. In the atrium, RS-100302 prolonged mean ERP (115+/-8 versus 146+/-7 ms, P<0.01) and wavelength (8.3+/-0.9 versus 9.9+/-0.8 cm, P<0.01), reduced dispersion of ERP (15+/-5 versus 8+/-1 ms, P<0.01), and minimally slowed conduction velocity (72+/-4 versus 67+/-5 cm/s, P<0.01). These effects were all partially reversed by cisapride. RS-100302 produced no ventricular electrophysiological effects. RS-100302 terminated atrial flutter in 6 of 8 animals and atrial fibrillation in 8 of 9 animals and prevented reinduction of sustained tachycardia in all animals.
Conclusions: The electrophysiological profile of RS-100302 suggests that it may have atrial antiarrhythmic potential without producing ventricular proarrhythmic effects.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1161/01.cir.100.19.2010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Investigating the Mechanisms Involved in Scopolamine-induced Memory Degradation.
Arch Razi Inst
June 2024
Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
In the present study, the mechanisms involved in scopolamine-induced memory impairment have been investigated. The molecular events that take place during memory mostly include mechanisms that are seen in the acquisition phase. Results showed that one of the mechanisms of memory destruction caused by scopolamine, in addition to weakening the cholinergic system, is the indirect effect of scopolamine on other neurotransmitter systems, including the glutamatergic system.
View Article and Find Full Text PDFTargeting serotonin receptors with phytochemicals - an in-silico study.
Sci Rep
December 2024
Department of Management, Bar-Ilan University, Ramat Gan, 5290002, Israel.
Article Synopsis
- * An evaluation of 88 phytochemicals identified five (Genistein, Kaempferol, Daidzein, Peonidin, and glycitein) with strong pharmacokinetic properties and effective binding to serotonin receptors.
- * The study suggests these phytochemicals, commonly found in soybeans and various plants, could lead to natural depression treatments, but more research is needed to confirm their effectiveness in real-world applications.
Zuojin Pill enhances gastrointestinal motility by modulating the pacemaker potentials in interstitial cells of Cajal through multiple signaling pathways.
Int J Med Sci
December 2024
Department of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
Article Synopsis
- Zuojin Pill (ZJP) is a traditional herbal remedy aimed at treating gastrointestinal disorders, and the study explores how it affects interstitial cells of Cajal (ICCs) and gut movement in mice.
- The research found that ZJP depolarizes ICCs, reducing their pacemaker activity and affecting calcium signaling, which is crucial for normal GI motility; this process is influenced by specific receptor interactions and various signaling pathways.
- Additionally, ZJP improved intestinal transit in mouse models of GI motility disorders and increased levels of key substances that promote gut movement, suggesting its potential as a therapeutic agent in digestive health.
Changes in hippocampal volume, 5-HT receptor binding, and verbal memory over the course of antidepressant treatment in major depressive disorder.
J Psychiatr Res
January 2025
Neurobiology Research Unit and BrainDrugs, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Mental Health Center Copenhagen, Copenhagen University Hospital - Mental Health Services CPH, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Article Synopsis
- - Serotonin reuptake inhibitors may help boost memory and increase hippocampal volume in patients with Major Depressive Disorder (MDD), particularly through the involvement of the 5-HT4 receptor. - In a study with 91 patients, significant reductions in hippocampal volume were observed after 8 weeks of treatment, especially in those responding well to the antidepressant escitalopram. - The research indicated a negative relationship between 5-HT4 receptor binding and hippocampal volume in females, suggesting a complex interaction that needs further exploration to understand its impact on memory and brain plasticity in MDD.
Electroacupuncture versus 5-HT4 receptor agonist for functional constipation: A systematic review and meta-analysis of randomized controlled trials.
Medicine (Baltimore)
November 2024
Department of Oncology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, China.
Background: Functional constipation (FC) has been found as a chronic gastrointestinal disease that is commonly diagnosed in patients. However, patients have a low satisfaction level with the treatment of constipation drugs (e.g.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!