Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore.

Psychedelic drugs can exert potent anti-inflammatory effects. However, anti-inflammatory effects do not appear to correlate with behavioral activity, suggesting different underlying mechanisms. We hypothesized that the distinct structural features of psychedelics underlie functionally selective mechanisms at the target 5-HT receptor to elicit maximal anti-inflammatory effects.

5-HT receptor activation alleviates airway inflammation and structural remodeling in a chronic mouse asthma model.

Aims: Although the bulk of research into the biology of serotonin 5-HT receptors has focused on its role in the CNS, selective activation of these receptors in peripheral tissues can produce profound anti-inflammatory effects. We previously demonstrated that the small molecule 5-HT receptor agonist (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] inhibits TNF-α-mediated proinflammatory signaling cascades and inflammation via 5-HT receptor activation and prevents the development of, and inflammation associated with, acute allergic asthma in a mouse ovalbumin (OVA) model. Here, we investigated the ability of (R)-DOI to reverse inflammation and symptoms associated with established asthma in a newly developed model of chronic asthma.

Activation of 5-HT Receptors Reduces Inflammation in Vascular Tissue and Cholesterol Levels in High-Fat Diet-Fed Apolipoprotein E Knockout Mice.

Coronary artery disease (CAD) is a progressive cardiovascular syndrome characterized by cholesterol-induced focal arterial lesions that impair oxygen delivery to the heart. As both innate and adaptive immune cells play critical roles in the formation and progression of arterial plaques and endothelial cell dysfunction, CAD is commonly viewed as a chronic inflammatory disorder. Our lab has previously discovered that 5-HT receptor activation with the 5-HT receptor selective agonist (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] has potent anti-inflammatory activity in both cell culture and whole animal models.