Drug-Receptor Model

Protein Structure

Theoretically drugs can bind to almost any 3-D target. Desired effects (as well as adverse effects) occur when drugs bind to selected target molecules or receptors. This binding causes biochemical or physiological changes within the body. Receptors are macromolecules that mediate the biochemical or physiological changes that occur when the drug binds.

Receptors are generally proteins. Proteins have 4 major levels of structure:

Different parts of the protein have different affinities for water:

Let's take a look at how protein structure develops:

Mod1_Slide04 image.jpg

Drug Binding

The binding site on a receptor is where the drug actually binds. Binding is affected by many different types of interactions:

Now let's view an animation on drug receptor binding:

This content requires Flash Player 10 or higher.

Get Adobe Flash Player

The animation above shows how drugs bind to cells.

The combination of all the interactions are what gives the drug its specificity. The favorability of the drug-receptor interaction is the affinity of the drug for the receptor (more later). Binding is rarely caused by one interaction. Stable Drug-receptor complexes usually have multiple interactions.

The molecular structure of a drug is what gives the drug its physical and chemical properties that determine how it will bind to the receptor. Important factors are:

Warfarin-S enantiomer 4x more potent vs. R enantiomer due to it's ability to bind to the receptor.

Let's take a look at a drug molecule as it binds to its receptor in a protein. In this case it inhibits the enzymes action, but drugs can also stimulate action.


Active Site

In some cases drugs bind to sites that have enzymatic activity. This active site is where enzymatic transformation is catalyzed. If the drug inhibits binding of the normal substrate is inhibits the enzymes action. In other cases the drug may not bind to the active site.

In these cases the drug may change the shape of the receptor to increase or decrease substrate binding. Drugs can also bind and change the conformation of the receptor referred to as induced fit:

The structure of a drug can affect its ability to get to the receptor because of the plasma membrane. Highly water-soluble drugs are generally less able to pass through the plasma membrane or they need membrane channels or transporters. Highly lipophilic drugs cross easily and have good access to intracellular targets.

Drug Design

Let's now look at the drug receptor relationship in an equation type relationship:

k1 = association constant (drug on)

k2 = dissociation constant (drug off)

k1 / k2 = AFFINITY


This equation represents a drug binding to a receptor and forming a drug receptor complex. Please note this is not a static process and may or may not elicit a response. We will talk more about this later in pharmacodynamics.

In general, the more restricted the cell-type distribution, the more selective the drug will be, and the more receptor-effector coupling mechanisms differ among the cell types targeted, the more selective the drug will be.

Receptor Types

Now we can take a look at 4 common types of receptors and get a visual idea of the process of drug binding to its receptor:



Let's look at regulation of an ion channel. This is an example of a Ligand-gated.


Now let's look at G-protein coupled receptors and what happens when an agonist binds to the receptor:


Here we'll take a look at how a steroid hormone can diffuse through the cell membrane to act at an intercellular target receptor:


Cellular Regulation

Now let's take a look at how cells can up regulate and down regulate receptors:


Not all drugs interact with receptors. Osmotic diuretics act on ion channels and change osmolarity of nephron directly. Antacids absorb or chemically neutralize acid.

Self Check Questions: Drug-Receptor Model

 Toggle open/close quiz question

Value: 1
All drugs work by binding to a receptor.

 Toggle open/close quiz question

Value: 1
Hydrophillic drugs can easily target cytosolic receptors.

 Toggle open/close quiz question

Value: 1
There are many types of receptors, but the most abundant is the transmembrane linked to intracellar G protein.

 Toggle open/close quiz question

Value: 1
The key factors that determine whether a drug can easily cross cellular membranes are: Check all that apply.

[mark all correct answers]

 Toggle open/close quiz question

Value: 1
There are many different types of forces that contribute to drug-receptor interactions. The strongest of these is?

Click to close