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Tretinoin binds to all 3 RAR’s. RARy, RARb, and RARa. This means its great for control keratinocyte turnover and keeping inflammation low, but the binding of RARa is where the problem comes. As i said, the binding of this receptor can lead to a lot of side effects. Most of the dryness, redness, and other irritable side effects from topical tretinoin come from the fact that tret binds to RARa.
How does adapalene differ?
You guessed it! Adapalene gel DOESNT bind to the RARa receptor, and only RARy and RARb. This is why adapalene is commonly tolerated better than tret. This binding profile means you get the correct shedding, anti-inflammation, and dead skin layer control benefits without the horrible, irritant side effects. The high selectiveness of adapalene gel in relation to its receptors cause it to provide less irritation.
Completely unique to it, adapalene inhibits AP-1 transcription factor and TLR signaling. In short, AP-1 increases pro-inflammatory cytokines and adapalene gel directly prevents the overexpression of those cytokines.