Antagonists

• Concentration effect curves for competitive agonists (reversible/ surmountable, non-reversible). Non-competitive inhibition (irreversible, allosteric, physiological antagonist)
• Reversible competitive antagonists dissociation constant
• Schild plot and the antagonist dissociation constant
• Antagonist K_B is independent of agonist affinity, efficacy, and potency
• IC₅₀ is potency, this is half the concentration of the antagonist which is required to reduce a maximal response by half.
• Inverse agonism and dependence on receptor activity

Learn.

Antagonists are substances that bind to a receptor and inhibit the function of the receptor. This can be both reversible and non-reversible binding.

As we saw before with the law of mass action, an increase in an agonist results in an increase in physiological response. However, over time this can result in someone developing tolerence to the drug. This is due to down regulation of the receptor. Commonly after rehab sessions or trips to prison. These receptor numbers will again increase, so when someone takes a drug like heroin. The amount they normally take would result in an overdose.

This overdose can be treated through drugs like naloxone which will act as an antagonist – blocking the receptors from taking in any more drug – this is an inverse agonist but will be covered in more detail later.

Inorder to notice the effect of an antagonist, an agonist must be present since it acts through inhibiting the activity of the agonist on the receptor. For surmountable antagonists they can be overcome by increasing the concentration of the agonist. This displaces them from the receptors resulting in no increase in maximal response. However, the concentration response curve will look indifferent to when there is no agonist present.

Dose response curve

• x_A is agonist concentration
• K_A is agonist dissasociation constant
• x_B is antagonist concentration
• K_B is antagonist dissasociation constant

• r for response at given concentration of x_A
• r_max for maximal response
• x_A is agonist concentration
• K_B is the disassociation constant for an antagonist
• EC50 is concentration for half a maximal response

Schild plot

A Schild plot allows us to determine whether the antagonist is competitive or not – if the gradient is one it is a competitive antagonist. In the case that we do have a competitive antagonist, we can then measure the affinity of the antagonist – this will be our x intercept in the form -pA₂. This means doubling the concentration of agonist will negate the effect of the antagonist.

By finding the 10 ^ (X intercept) of the Schild plot, we find the K_B value.

plot the the log of concentration of our Antagonist

• r_A is the EC50 with the antagonist present/ EC50 without the antagonist present.
• K_B is the disassociation constant for an antagonist
• x_B is antagonist concentration

Memorize.

Master.