Background: Esophageal involvement in systemic sclerosis (SSc) carries significant morbidity and is empirically managed with domperidone, albeit with questionable efficacy. The oral 5-HT 1A receptor agonist buspirone may enhance esophageal peristalsis and lower esophageal sphincter (LES) function in healthy volunteers. Aim: We aimed to test the hypothesis that buspirone may exert a beneficial acute effect on esophageal motor dysfunction in symptomatic patients with SSc. Methods: Twenty consecutive patients with SSc reporting esophageal symptoms underwent high-resolution manometry before and 30 minutes after administration of buspirone (10 mg). Ten other patients received domperidone (10 mg) and served as control group. Changes in LES resting and residual pressure, amplitude, duration, and velocity of distal esophageal body contractions were examined. Results: Esophageal hypomotility and hypotensive LES was found in 63% and 67% of patients, respectively. Demographic and clinical characteristics, including baseline manometric parameters, were comparable between groups. Resting pressure of LES increased after buspirone from 9.42 AE 2.6 to 11.53 AE 3.4 mmHg (p ¼ 0.0002 by paired t-test), but not after domperidone; a trend for increase of amplitude of contractions was also observed after buspirone (p ¼ 0.09). Comparison of the individual changes revealed that buspirone was superior to domperidone in enhancing LES pressure ( þ 2.11 AE 2.0 versus -0.45 AE 2.3 mmHg, p ¼ 0.006). No significant effects of either drug were noted on other examined parameters of esophageal function. Conclusion: The beneficial acute effect of buspirone on impaired LES function associated with SSc suggests a role of 5-HT 1A receptor-mediated interactions in these patients. Prospective studies to examine whether buspirone is of long-term therapeutic value for SSc-associated esophageal disease are warranted.

Background: Acute administration of the oral 5-HT 1 A receptor agonist buspirone, which is commonly used as an anxiolytic drug, may improve compromised lower esophageal sphincter function. In an open-label trial we assessed the effects of buspirone on esophageal motor function and symptoms in patients with esophageal involvement associated with systemic sclerosis (SSc). Methods: Thirty consecutive patients with SSc and symptomatic esophageal involvement, despite treatment with proton pump inhibitors, underwent high resolution manometry and chest computed tomography for assessment of motor function and esophageal dilatation, respectively. Regurgitation, heartburn, dysphagia, and chest pain severity was subjectively scored by visual analog scales. Manometric parameters (primary endpoint) and symptom severity (secondary endpoint) were re-examined after 4-week daily administration of 20 mg buspirone. Other medications remained unchanged. Results: Eight patients did not complete the trial because of buspirone-associated dizziness (n = 2), or nausea (n = 2), or reluctancy to undergo final manometry. In the remaining 22 patients lower esophageal sphincter (LES) resting pressure increased from 7.7 ± 3.9 to 12.2 ± 4.6 mmHg (p = 0.00002) after buspirone administration; other manometric parameters did not change. Statistical analysis revealed negative correlation between individual increases in resting LES pressure and supra-aortic esophageal diameter (r = -0.589, p = 0.017), suggesting a more beneficial effect in patients with less severely affected esophageal function. Heartburn and regurgitation scores decreased at 4 weeks compared to baseline (p = 0.001, and p = 0.022, respectively).

Moxonidine is the newest, second-generation, centrally acting antihypertensive agent. It has selective agonist activity at imidazoline I1 receptors and less adverse effects than the other centrally acting drugs. This fact authorizes the frequent use of moxonidine in clinical practice, as monotherapy or in combination with other antihypertensive agents. Also, moxonidine has beneficial effects in obese and metabolic syndrome and in target-organs, such as heart and kidneys.

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Background Domperidone is widely used for the management of symptoms in patients with Systemic Sclerosis (SSc) and esophageal involvement, but its efficacy is under question. Recently, buspirone, an orally available 5-HT1A receptor agonist, was shown to enhance esophageal peristalsis and lower esophageal sphincter (LES) function in healthy volunteers (Di Stefano M et al, Dis Esophagus. 2012 Jul;25(5):470-6) Objectives To evaluate the effects of acute buspirone and domperidone administration in SSc patients with symptomatic esophageal involvement. Methods Thirty consecutive patients (26 women, aged 52.3±10.4 years, 15 and 15 with diffuse or limited SSc, respectively) underwent high resolution esophageal manometry (HRM) before and 30 minutes after randomised administration of 10 mg buspirone (n=19) or 10 mg domperidone (n=11). We compared buspirone and domperidone effects, before and after drug administration, on: a) resting pressure of the LES; b) residual pressure of LES relaxation; c) amplitude, duration, and onset velocity of esophageal body contractions. Prior to HRM each patient completed a self-reported 0-100 visual analogue scale questionnaire for esophageal symptoms (ESQ). Results There was no difference in terms of SSc characteristics, as well as of clinical severity (assessed by ESQ scores) and extent (assessed by HRM findings) of esophageal involvement between patients who received buspirone or domperidone. Buspirone increased mean resting pressure of LES (from 9.42±2.6 to 11.53±3.4 p<0.001 by paired t-test), whereas domperidone’s effect was not significant (from 9.09±3 to 8.64±2.6, p=0.469). Comparison of the mean individual changes after administration of either drug revealed that buspirone was superior to domperidone in enhancing the resting pressure of LES ( +2.11±2.0 versus -0.45±2.3, p=0.006 ). Neither buspirone nor domperidone had any significant effect on the other examined parameters of esophageal function. Conclusions Acute administration of buspirone, but not of domperidone, exerted a beneficial effect on impaired LES function in patients with SSc, suggesting a role of 5-HT1A receptor-mediated interactions in these patients. Prospective studies to examine whether buspirone is of long-term therapeutic value for SSc-associated esophageal disease are warranted. Disclosure of Interest: None Declared

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