Acetaminophen: A new mechanism of action involving the cannabinoid pathway may widen its utility to neurodegenerative disorders? The market for over the counter pain medications is massive (see for example The US Market for OTC Pain Medication). Acetaminophen, commonly referred to by its brand names Tylenol and Paracetamol, is often the first drug used for control of mild to moderate pain especially when aspirin is contraindicated. Although acetaminophen has been used as an analgesic for well over 100 years its mechanism of action is unclear. Today’s featured article reports data using the hot plate assay suggesting that the analgesic effect of paracetamol is prevented by cannabinoid CB1 receptor antagonism. This study suggests that acetaminophen somehow activates the cannabinoid pathway and this is consistent with a second recent study (Hoggestat et al, 2005) reporting that acetaminophen, following deacetylation to its primary amine, is conjugated with arachidonic acid in the brain and the spinal cord to form the N-arachidonoylphenolamine (AM404). This molecule in turn is well known as an endocannabinoid reuptake inhibitor; in other words acetaminophen may exert analgesic effects through the amplification of endogenous cannabioid pathways. Considering the blockbuster potential and multiple indications of cannabinoid therapeutics (see Cannabinoids - A potential blockbuster market), based on these two studies the benefit of paracetamol or molecules modelled on its chemical structure may extend past one of analgesia. Of note CB1 receptor activation may be of interest for the treatment of multiple sclerosis or Parkinson’s disease. Since acetaminophen appears to be converted to AM404 in the brain an intriguing possibility arises that paracetamol may increase CB1 receptor activation by preventing cannabinoid metabolism in a highly selective fashion in the brain circumventing problems associated with nonselective cannabinoid receptor activation in the periphery.

http://leaddiscovery.blogspot.com/2006/05/acetaminophen-future-of-multiple.html

yea, i know its a year  old,  but i still thought it was cool anyway.

~KM