Amarin Corp Plc (AMRN)

[Biobillionair]

Has anyone noticed, after being on Vascepa, how potent ibuprofen is when taken as needed?
I did. It lead me to a couple hours of Biochem and Dr. Sears research.

This is a very simplified mechanism of action diagram:
http://www.lef.org/magazine/mag2007/images/ss2007_report_epa_dha_04.jpg

More detailed stuff:
http://t3.gstatic.com/images?q=tbn:ANd9GcQ9_N3ooeDb_awhYxMRfrdauOzOLkJ_34PSry1pxnFIr6jrfIlQ

My understanding:When the "membrane Phospholipid layer" of your cells is damaged, this sets in motion a cascade of enzymatic events.
1)Injury & cell damage
2)Increase in Arachidonic Acid production
3)"Arachidonic acid is one of the chemicals released during tissue damage. It is then metabolized into prostaglandin (and cytokines). The action of the prostaglandins is mediated through a G protein, protein kinase A cascade. The prostaglandins block the potassium efflux released from nociceptors following damage, which results in additional depolarization. This makes the nociceptors more sensitive. Aspirin is an effective pain killer because it blocks the conversion of arachidonic acid to prostaglandin."http://neuroscience.uth.tmc.edu/s2/chapter06.html

So where the heck does EPA fit in, exactly. The answer is hard to find, but easy to understand when you find it. FDA documents are blanked out, several studies don't make mechanisms known. Had to dig into Dr. Sears, the man is a freaking genius! JL, always thought you where a little nutty when you mentioned some of this. This is real science not taught to those that need to know and understand these pathways.

EPA's mechanism of action with Arachidonic Acid:
1) EPA inhibits the production of Linolenic Acid production. This is done by inhibiting Delta-5-desaturase enzyme, this is the enzyme that converts alpha-Lionolenic Acid (Omega-6) into AA. The end result is less AA and less prostaglandins production responsible for pain.

2) EPA inhibits PLA2, PLA2 is another enzyme that can convert Free FA to AA. Thus, reducing AA production via a completely separate mechanism from 1.

So, when you combine a COX1 inhibitor (aspirin), COX2 inhibitor (ibuprofen), and EPA you get a MASSIVE reduction in AA production with tissue damage (pain causing event). So how much? Well, the prescription COX2, ketorolac 30 mg IV, is equivalent to about 6 mg of Morphine given IV, without the opioid side effects of respiratory depression, GI, and CNS effects...I'm guessing a premedication dose of 2-4 grams of Vascepa and IV Tylenol/ketoroalc would be very successful in the reduction of postop pain management.

Or a combo aspirin/Tylenol/ibuprofen/EPA mix, maybe the equivalent of 10 mg Morphine IV "over the counter".

Williams