Electrophysiological and Antiarrhythmic Effects of the Atrial Selective 5-HT ₄ Receptor Antagonist RS-100302 in Experimental Atrial Flutter and Fibrillation

Q1 · MEDICINE

Article

Author: Feld, Gregory K. ; Wadhwa, Manish K. ; Eglen, Richard M. ; Leistad, Elisabeth ; Rahme, Marc M. ; Mohabir, Rajendra ; Cotter, Bruno ; Ford, Anthony P. D. W.

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.

100 Deals associated with RS-100235

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Arrhythmias, Cardiac	Phase 1	-	F. Hoffmann-La Roche Ltd.	-
Irritable Bowel Syndrome	Phase 1	US	Roche Palo Alto LLC	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

RS-100235

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation