Anti‐inflammatory effects of serotonin 5‐HT 2A receptor activation in ovalbumin‐induced allergic asthma models

Activating the 5-HT2A receptor with the agonist (R)-DOI before allergen exposure reduces airway hyperresponsiveness in a chronic mouse model of allergic asthma, suggesting a potential new treatment for inflammatory airway diseases. The authors previously showed that (R)-DOI prevents asthma symptoms in an acute ovalbumin-induced model, and here they extend those findings to a persistent asthma model. They also report testing psilocybin and other tryptamines for effects on airway hyperresponsiveness in rodents. The overall goal is to develop 5-HT2A receptor agonism as a therapy for asthma and related inflammatory disorders.

Study at a glance

Abstract

Only recently has the full therapeutic value of serotonin [5‐hydroxytryptophan (5‐HT)] receptor activation begun to be explored. Currently there are two 5‐HT 2A receptor agonists in human clinical trials for the treatment of depression and obesity. An exciting new therapeutic avenue in which 5‐HT 2A agonists might be employed is the modulation of inflammation in allergic airways disease. Our lab has previously used an ovalbumin (OVA)‐induced asthma model to demonstrate that administration of (R)‐2,5‐dimethoxy‐4‐iodoamphetamine [(R)‐DOI] prior to allergen challenge prevents many of the symptoms of allergic asthma. Here we have utilized a modified protocol to test the effectiveness of (R)‐DOI in treating persistent allergic asthma. We demonstrate that administration of (R)‐DOI in a chronic model attenuates the elevated airway hyperresponsiveness (AHR) typically observed in an asthmatic response. We also have probed for the expression of inflammatory markers in the lung and BALF. We concurrently are testing for the impact psilocybin and other tryptamines have on AHR in rodents using our OVA model. Overall our strategy is to develop 5‐HT 2A receptor agonism as a viable treatment modality against asthma and other inflammatory disorders. Support or Funding Information American Asthma Foundation Scholar Grant Award