Question 1

College Answer

A good answer provided a definition of a receptor as a protein/glycoprotein that undergoes a conformational change upon ligand binding. They then gave an overview of where these are found and the mechanisms of activitation/downstream processing. A definition of each type (agonist, antagonist, partial agonist and inverse agonist) was expected with reference to the intrinsic activity at the receptor and the affinity for the receptor. A good answer also touched upon law of mass action (D+R=DR) and how this equilibrium is altered by each. Concepts such as reversible and irreversible binding and its implications as well as competitve and non-competitive antagonism would elevate the answer.

Discussion

a)

• "Receptors are cellular macromolecules, or assemblies of macromolecules, that are concerned directly and specifically in chemical signaling between and within cells" - International Union of Pharmacology Committee on Receptor Nomenclature
• Drugs interact with receptors  to produce a change in the state of the receptor, which is then translated into a physiological effect directly or via secondary messenger systems.
• This molecular interaction with the receptor can be modelled mathematically and obeys the Law of Mass Action.

b)  "the relationship between the properties of a drug and potential receptor response" is hard to parse. As the examiners mention that "a definition of each type was expected", perhaps a better wording would have been "define the following, with reference to the intrinsic activity at the receptor and the affinity for the receptor".  That might look like this:

• Agonists: ligands that binds to a receptor and alter the receptor state resulting in a biological response.
• Partial agonists: ligands that, even at full receptor occupancy,  cannot elicit as large an effect as can another agonist.
• Inverse agonists: ligands that by binding to receptors reduce the fraction of them in an active conformation, if some of the receptors are in the active form in the absence of a conventional agonist
• Antagonists: ligands that reduce the action of another ligand. 
  • A competitive antagonist competes for the same binding site with an agonist, and their binding is mutually exclusive
  • A non-competitive antagonist can prevent the action of an agonist without any effect on the binding of the agonist to the receptor.
  • An insurmountable antagonist can reduce the maximum effect of the agonist, and this inhibitory effect is not affected by increasing agonist concentration. 
  • An irreversible antagonist is insurmountable, but it does not  have to be non-competitive 

Neubig, Richard R., et al. "International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology." Pharmacological Reviews 55.4 (2003): 597-606.

Rang, H. P. "The receptor concept: pharmacology's big idea." British journal of pharmacology 147.S1 (2006).

Kenakin, Terry. "Principles: receptor theory in pharmacology." Trends in pharmacological sciences 25.4 (2004): 186-192.

Pleuvry, Barbara J. "Receptors, agonists and antagonists." Anaesthesia & Intensive Care Medicine 5.10 (2004): 350-352.

Ariens, E. J. "Intrinsic activity: partial agonists and partial antagonists." Journal of cardiovascular pharmacology 5 (1983): S8-15.

Kenakin, Terry. "Agonists, partial agonists, antagonists, inverse agonists and agonist/antagonists?." Trends in Pharmacological Sciences 8.11 (1987): 423-426.