Why is there structural similarity between agonists but diversity in antagonists?

[kidamnesiac]

Title should be clear, a question that I have some ideas about but is part of a question I'm trying to answer for a paper and would like some insight from the heads here.

 

[haribo1]

Can you give an example? Opiate antagonists, for example, are just like agonists apart from the N-substitution. Benzo antagonists still have an underlying benzo pattern. What class are you thinking of?

 

[kidamnesiac]

for instance, and this is not even what im thinking of, but 5-HTx antagonists can be all over the place, but the agonists are of a reasonably similar nature (with obvious exceptions to the rule)

 

[vecktor]

Title should be clear, a question that I have some ideas about but is part of a question I'm trying to answer for a paper and would like some insight from the heads here.

I assume we are talking competitive antagonists, though to an extent non competitive antagonists also play by the same rules anyway....

Because an agonist has not only to bind but also has to bind in a way that allows the active conformation which is quite restrictive. antagonists on the other hand just have to bind in any way that blocks the binding site of the agonist, they can bind in various orientations and can have shrubbery that interacts with other parts of the receptor
to use the locked door analogy, the door agonist is the key, which has to be able to turn the lock, the other can be anything that blocks the lock or fills the keyhole... chewing gum or a lump of wood banged into the keyhole are structurally diverse door antagonists.

I guess too that on the whole agonists are necessarily smaller and therefore simpler than the antagonists, less room for modification on an agonist.

I will think on this some more........

 

[kidamnesiac]

chewing gum a lump of wood banged into the keyhole are structurally diverse door antagonists.

awesome :D

and thank you

 

[Jamshyd]

Wait! So this mean that if I eat chewing gum on a lump of wood, I would not be able to get effects from drugs?

J/k... excellent analogy, vecktor!