Comment · Tue, November 22, 2022 · ND Owner
Where We're Going, We Don't Need Roads
What they were answering
nahin123 · 2 points
Could you please ELI5 what’s the difference between PAMs and agonists?
u/MisterYouAreSoDumb · ND Owner
Positive allosteric modulators increase the activation of a receptor without actually binding to the main site of the receptor. PAMs interact with binding sites that are distinct from the orthosteric site recognized by the receptor's endogenous agonist. Take 5-HT2A for example. Serotonin binds directly to that receptor at its orthosteric (active) binding site. However, a 5-HT2A PAM will bind to a distinct separate site on the receptor complex, which will alter the structure of the receptor in such a way that it makes it more likely for endogenous serotonin to bind, or result in stronger signal cascades after binding. However, it is still the endogenous serotonin your body is making that is activating the receptor, so your body's rate-limiting processes still control the max level of activation. Very simply, PAMs increase the activity of a receptor to its natural ligand, where agonists actually displace the natural ligand and activate the site directly.