FOCUS on Drug MOA. The mechanism of action of acetaminophen has been determined by a group led by Avi Priel at the Hebrew University, Jerusalem, and is out in the current issue of PNAS. Acetaminophen (paracetamol) is trans-acylated with arachidonic acid in primary sensory neurons, producing a metabolite known as AM-404. AM-404 then selectively blocks voltage-gated sodium channels (Nav1.7 and 1.8), resulting in reduction of normal and inflammatory pain.
AM-404 was first synthesized decades ago by Alexander Makriyannis as part of a program to explore the SAR of anandamide.
