The Ameliorating Effect of ST-6631, Novel TRPV1 Agonist, in Dysphagia Animal Model (P3-5.011)

This study aimed to assess the recently acquired TRPV1 agonist called ST-6631 by utilizing an animal model. The objective was to explore its potential as a new drug for dysphagia. Dysphagia poses not only a detriment to one's quality of life but also gives rise to life-threatening situations like choking and aspiration pneumonia. Despite these risks, no effective medications exist, and no compounds have been developed for the treatment of swallowing disorders. Male Sprague-Dawley rats were employed for this investigation. In the eye-wiping test, the number of wiping of the right eye was recorded for one minute. To assess the swallowing frequency, normal rat and dysphagia model through occlusion of the common carotid artery were utilized as the experimental model. Bilateral occlusion of the common carotid arteries (BCAO) was performed under anesthesia. A vehicle, ST-6631 dosing solution, or capsaicin dosing solution was infused into the pharynx region, under urethane. The number of swallowing reflexes was then recorded for one minute, starting from the initiation of the dosing solution infusion. Capsaicin demonstrated a significant increase in the number of eye wipes at concentrations of 10 μM and higher, compared to the vehicle group. Conversely, no significant effect was observed with ST-6631, even up to 1000 μM. Subsequently, we examined the impact on inducing the swallowing reflex. Both capsaicin and ST-6631 exhibited a significant increase in the number of swallows in normal and BCAO rats. The present results suggest that ST-6631, a novel TRPV1 agonist, ameliorates the swallowing reflex comparable to capsaicin in dysphagia model. Previous evidence for capsaicin suggests that TRPV1 agonists improve dysphagia when administered in conjunction with mealtimes. ST-6631 has the potential to become the first swallowing treatment without irritating. Disclosure: Dr. Miyauchi has nothing to disclose.