Antagonists bind (have affinity) but do not activate he receptor so they do not have any

intrinsic efficacy. All drugs have potency.

Antagonists can elicit a response in the body by preventing receptor activation by

endogenous chemicals. The effect is only observed when an agonist is present however.
- No efficacy in vitro
- Active in vivo (clinical efficacy) // therefore has a measurable potency
Compete with agonists for the receptor.
Competitive surmountable antagonism – as the concentration of the antagonist is increased
there is a parallel rightward shift. The maximum is unchanged. Reduce potency = more
agonist for the same effect.
Antagonist dissociation constant (KB) can be derived from:
- Direct binding assays
- Schild plot
- pA2 // How much antagonist do you need to shift the curve two-fold, to double to
concentration of agonist? It is an indication of antagonist potency
Not all antagonists are surmountable | If not surmountable, maximum depressed rightward
shift, not parallel.
Competitive insurmountable antagonism – The same antagonist gives different effects on
full and partial agonists acting at the same receptor. Maximum response decreases
immediately if there are no spare receptors.
Pattern of antagonism is determined by:
- KD (association/dissociation constants)
- Concentration
- Duration of exposure
Binding of antagonist is slowly reversible/ irreversible:
- Strong binding, very high affinity
- Antagonist effectively candecreases the number of the receptors