Effects of ondansetron on respiratory pattern and sensation of experimentally induced dyspnea

Abstract

CONTEXT: Dyspnea remains a therapeutic challenge, especially in chronic respiratory conditions. Recent studies have shown that the induction of unpleasant dyspnea sensations activates areas in the insular cortex. OBJECTIVE: This study was designed to investigate the potential effects of ondansetron, a potent anti-serotonin agent, on induced dyspnea sensation. TYPE OF STUDY: A randomized double blind study. SETTING: Pulmonary Function Laboratory of Hospital das Clínicas de Ribeirão Preto. PARTICIPANTS: Ten healthy male volunteers (mean age ± standard error = 23.1 ± 0.41 years) without respiratory diseases and showing normal spirometric tests. INTERVENTIONS: Uncomfortable breathing was induced in the volunteers on two different days, via the use of inspiratory resistors (loads of 0, 7, 14 and 21 cm H2O/l/sec) and breathholding, two hours after taking 8 mg of ondansetron (Ond) or placebo (Plac). MAIN MEASUREMENTS: Respiratory discomfort during breathing under loading was evaluated on a 100-mm visual analog scale. The maximum length of time of voluntary apnea was measured in seconds. RESULTS: The mean maximum voluntary apnea time did not differ between the ondansetron and placebo days (Plac = 96 ± 6.6 sec vs. Ond = 100 ± 7.9 sec). Ondansetron did not influence the dyspnea sensation induced by different inspiratory loads (0 cm H2O/l/sec: Ond = 1.4 mm ± 0.44 vs. Plac = 2.1 ± 0.85 mm; 7 cm H2O/l/sec: Ond = 16.6 ± 2.74 mm vs. Plac = 13.7 ± 2.06 mm; 14 cm H2O/l/sec; Ond = 30.5 ± 4.50 mm vs. Plac = 27.1 ± 3.44 mm; 21 cm H2O/l/sec: Ond = 50.3 ± 6.72 mm vs. Plac = 49.4 ± 6.72 mm). Ondansetron led to significant decreases in tidal volume under basal conditions and when breathing under the highest inspiratory loading (0 cm H2O/l/sec: Ond = 0.83 ± 0.26 l vs. Plac = 1.0 ± 0.28 l; 21 cm H2O/l/sec: Ond = 0.86 ± 0.23 l vs. Plac = 1.1 ± 0.22 l) CONCLUSION: The present results suggest that 5-HT3 receptors do not play an important role in the mediation of dyspnea sensations.

Ventilatory Dysfunction in Parkinson’s Disease

“…Although there is still a doubt about the role of serotonin [20], anti-inflammatory drugs like steroids may interfere in dyspnea sensation [21]. After the administration of L-DOPA, improvements in lung function were not correlated with the reduction in the symptoms reported by the patients [15].…”

Non-opioid medications for the relief of chronic breathlessness: current evidence

“…24 25 26 Exploratory work investigated its potential role as a modulator of chronic breathlessness working on the insular cortex in a small RCT (n=10) , but showed no benefit in healthy volunteers with experimentally induced acute breathlessness. 27 A study of inhaled ondansetron (8 mg) compared to inhaled 0.9% saline in healthy subjects in whom acute breathlessness was induced by thoracic constriction and exercise [NCT01851993] is ongoing. It is not known how such findings will apply to the context chronic breathlessness.…”

Physiologic changes and clinical correlates of advanced dyspnea

“…One hypothesis that can be generated from these data is that improvements in emotional state, or alternatively measures of distraction, may cause less dyspnea and at the same time, result in objective improvement in exercise capacity. The effect of emotions on dyspnea is far from clear, however; the little direct information available suggests that anxiolytic and antidepressant drugs improve mood in dyspneic subjects, but may not improve dyspnea (23-26). This source of apparent inconsistency may be due to failure to measure the appropriate dimensions of dyspnea (27)…”