I'm rather new to neuropharmacology, and I am particularly interested in why some psychotropic medications are more potent than others despite being in the same category of one another, (i.e.: Oxymorphone, and Etorphine being both opioids) and acting as agonists at the same receptors. I am aware that binding affinities determine the potency and strength of a drug. E.g.:
Morphine has an affinity of 1.8 nM (Ki) on the MORs. Whereas Fentanyl has a binding affinity of 0.39 nM (Ki) on the MORs. And so therefore, fentanyl requires a far lower dose than morphine for the patient receiving fentanyl to sustain adequate analgesia.
How are these two, totally structurally different opioids, able to agonise the same receptors, and how do the structures of them make one more potent than the other? A similar question goes for the following Drugs:
Why are most Triazolobenzodiazepines, such as: Clonazolam, Flunitrazolam, and Triazolam far more potent in their dose, and effects, then Benzodiazepines such as: Chlordiazepoxide, Nitrazepam, and Diazepam?
Why do small changes in the skeletal structure of psychoactive drugs have such a large impact on binding affinities?