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Effects of ondansetron on respiratory pattern and sensation of experimentally induced dyspnea
José Antônio Baddini Martinez1, Fábio Senra Rocha, Elizabet Sobrani
1Departamento de Medicina Interna, Faculdade de Medicina de Ribeirão Preto, São Paulo, Brazil. jabmarti@fmrp.usp.br
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.
Insights
Ondansetron, an anti-serotonin drug, did not alter the sensation of dyspnea or apnea time in healthy volunteers. These findings suggest serotonin 5-HT3 receptors are not key in mediating breathing discomfort.
Area of Science:
- Respiratory Physiology
- Neuropharmacology
Background:
- Dyspnea is a challenging symptom in chronic respiratory diseases.
- Dyspnea sensation activates the insular cortex.
Purpose of the Study:
- To investigate the effect of ondansetron, a 5-HT3 receptor antagonist, on induced dyspnea.
- To determine the role of 5-HT3 receptors in dyspnea perception.
Main Methods:
- Randomized, double-blind, placebo-controlled study.
- Healthy male volunteers underwent induced dyspnea using inspiratory resistors and breath-holding.
- Dyspnea sensation and apnea time were measured after ondansetron or placebo administration.
Main Results:
- Ondansetron did not significantly affect dyspnea sensation across various inspiratory loads.
- Mean maximum voluntary apnea time was similar between ondansetron and placebo conditions.
- Ondansetron decreased tidal volume under basal and loaded breathing conditions.
Conclusions:
- Serotonin 5-HT3 receptors do not appear to play a significant role in mediating dyspnea.
- Further research is needed to fully elucidate the neurobiological pathways of dyspnea.
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