What is a noncompetitive antagonist?

Answer: In pharmacology, a noncompetitive antagonist decreases the downstream action of a receptor after agonist binding.

From http://employees.csbsju.edu/hjakubowski/classes/ch331/transkinetics/olinhibition.html

From http://employees.csbsju.edu/hjakubowski/classes/ch331/transkinetics/olinhibition.html

When neurotransmitter is released, it can activate a receptor at the postsynaptic membrane. The neurotransmitter is referred to as the agonist in this interaction. The agonist binds of a highly specific site on the receptor protein, much like a key into a lock. This site where the agonist binds is the active site. Once the agonist binds to the active site, a change in the structure of the protein allows the postsynaptic response to occur. Interaction of an agonist with the receptor depends on random movement of molecules, following the laws of Brownian motion.

A noncompetitive antagonist acts at an allosteric site, away from the active site. The noncompetitive antagonist can change the downstream response after an agonist binds to the active site. Because it acts at a different location, increasing the amount of agonist will not overcome the presence of the noncompetitive antagonist.

A dose response curve is helpful to visualize the action of many pharmacological agents. This plots the pharmacological effect of a drug on the y-axis (response) and the concentration on the x-axis (dose). Addition of a noncompetitive antagonist would shift the peak of the dose response curve downwards.

Compare this with a competitive antagonist, which interacts directly with the active site. Because the competitive antagonist acts at the same molecular site as the agonist, it is possible to add a very high concentration of agonist to overcome whatever concentration of antagonist is present. Addition of a competitive antagonist shifts the dose response curve to the right.