Squeege, what do you think about this, (is a disscussion from hair site about indomethacin):
It seems that many people are unfamiliar with the word "agonist".
Indomethacin is a CRTH42 agonist, not an antagonist.
An AGONIST is the exact opposite of an antagonist.
An antagonist inhibits the action of the receptor. An agonist actually
promotes or activates the receptor.
This is exactly what you DON'T want.
I have been following this site for a while and also buy bodybuilding related products from ID.
I know a little bit about how they work based on interactions in the past and can say they do not
put out products that are not well thought out.My biochem background also helps.
It appears indomethacin is included in the formulation for its effects on PGD synthase, which is significant.
Local expression of PGD2 will be reduced by reducing PGD synthase and mast cell release of PGD2.
Whether this will only halt balding or whether it will induce regrowth is impossible to say.
As for the agonist effect of indomethacin, this is why I joined the site - because sometimes
it gets old hearing things get repeated by those who do not fully understand them.
Dude, you may know enough to explain what an agonist is, but it is clear you either
don't have the knowledge or the willingness to dig deeper.
Click this study and follow along:
http://www.jimmunol.org/content/168/3/981.long
Now, IC50 and EC50 are terms used primarily in in vitro studies. IC50 is the concentration required
to inhibit 50% of the effect at the receptor level of 50% of a given effect observed. EC50 stands
for excitatory concentration, and is the opposite (required for activation of an effect.
From the study - there is some competitive effect, see below:
"indomethacin indeed inhibited [3H]PGD2 binding to K562/CRTH2 cells with the lowest IC50 value (8.1 ± 1.9 μM) among NSAIDs examined"
Now the agonist effect may be of concern, but the question becomes how potent the agonist is.
Some agonists are weak and others are strong... the ratio of activity compared to the usual ligand (in this case PGD2) is significant.
The below indicates a relative potency for chemotaxis (compared to PGD2) of about 1/20-1/50, though this excerpt does not speak to receptor binding directly:
"CRTH2-transfected Jurkat cells (Jurkat/CRTH2) were indeed attracted by indomethacin and PGD2 (approximate EC50, 50 nM and 1 nM, respectively)
but mock-transfected Jurkat cells (Jurkat/neo) were not (Fig. 3⇓A). DP-transfected Jurkat cells (Jurkat/DP) were suppressed in their spontaneous migration by PGD2,
as shown previously (8), but not by indomethacin (Fig. 3⇓A). Indomethacin and PGD2 also induced chemotactic migration of Th2 but not Th1
cells at submicromolar concentrations (EC50, 50–100 nM and 2–3 nM, respectively; Fig. 3⇓B)."
The below is a better indicator of the relative potency of indomethacin as opposed to PGD2...
"Indomethacin induced Ca2+ mobilization in K562/CRTH2 cells at submicromolar concentrations (approximate EC50, 50 nM) with around one order of magnitude lower potency than that of PGD2;"
This means one of two things. If receptor binding is equal or indomethacin is graeter, the fact that indomethacin is about 1/10 as potent as PGD2 (a "weak agonist" could be almost as good as an inhibitory effect.
If it is not equally strong-binding, which is likely the case, then its effects on the receptor are very minimal
to the point of being insignificant IF PGD2 is already active there (and the whole assumption of this thread is that that is the case in bald men).
The fact is that a receptor-binding antagonist is necessary in a formulation with or without indomethacin.
Seeing as this is the first PGD2 inhibitor product availalble, it was probably put out to meet demand - I would not be surprised
if subsequently the product improves, or competitors pick up on this.
However, the supposed agonist activity of indomethacin is not likely as significant a factor as the inhibitory effect on PGD synthase.
In allergy models of PGD2 inhibition it is equally effective to many CRTH2 receptor antagonists in efficacy; if it stimulated CRTH2 receptors in a meaningful way it would not likely be that effective.
