Michael J. Forrest

TL;DR: Data suggest that the recruitment and activation of macrophages and microglia peripherally and in neural tissue may contribute to both inflammatory and neuropathic pain states, and blockade of the CCR2 receptor may provide a novel therapeutic modality for the treatment of chronic pain.

TL;DR: The development of a COX-2 inhibitor rofecoxib (MK 966, Vioxx) is described, essentially equipotent to indomethacin both in vitro and in vivo but without the ulcerogenic side effect due toCOX-1 inhibition.

TL;DR: Rofecoxib is a novel COX-2 inhibitor with a biochemical and pharmacological profile clearly distinct from that of current nonsteroidal anti-inflammatory drugs and represents a new therapeutic class of anti- inflammatory agents for the treatment of the symptoms of osteoarthritis and rheumatoid arthritis with improved gastrointestinal tolerability.

TL;DR: Three lines of evidence link S1P3 receptor activity with acute toxicity and cardiovascular regulation: compound potency on S 1P3 correlated with toxicity and bradycardia; the shift in potency of phosphorylated-FTY720 for inducing lymphopenia versus brady Cardia and hypertension was consistent with affinity for S1 p1 relative to S1p3; and toxicity, brady cardia, and hypertension were absent in S1 P3-/- mice.

TL;DR: There was an excess of deaths and adverse cardiovascular events in patients taking torcetrapib, and the studies reported herein sought to evaluate off‐target effects of torcETrapib.