Agonists and Antagonists

Chemical Antagonist

Interact directly with the drug/agonist - Remove the drug from the system -Prevent the drug from binding to its receptor

Emax

Maximal effect of the drug This is an indicator of efficacy

Affinity

Measure of the ability of the drug to bind its receptor site Drugs with a higher affinity are usually more potent. The smaller the Kd, the greater the affinity

noncompetitive and irreversible antagonists

Reduce Emax by reducing available receptors

Inverse Agonist vs. Antagonist

-Increasing concentrations of inverse agonist alone produces an effect. -Increasing concentrations of antagonist produces an effect only in the presence of an agonist.

Graded dose-response curve

A graph of increasing response to increasing drug concentration or dose

Quantal dose-response curve

A graph of the fraction of a population that shows a specified response at progressively increasing doses

Agonist

Any drug/chemical molecule that binds a receptor and produces an effect -The magnitude of the drug effect is proportional to the amount of drug:receptor complexes formed.

Antagonist

Any drug/chemical molecule that blocks the effect of an agonist

Describe the effect of adding a competitive antagonist to an agonist

Competitive antagonist shifts the agonist dose-response curve to the right, increasing EC50 (agonist appears less potent)

Potency

Indication of the amount of drug needed to produce a given effect Defined by the EC50 of the drug The smaller the EC50, the greater the potency

EC50

Drug dose or concentration that produces 50% of the maximal effect

3 types of agonists

Full agonists Partial agonists Inverse agonists

Allosteric modulators

Have no direct activity on their own Alter the affinity of the agonist for the receptor or the level of receptor activation after agonist binding

Describe the effect of partial agonists in the presence of agonists

They act like antagonists, reducing the Emax (efficacy) of the agonist by reducing the number of available receptors

allosteric inhibitor/antagonist

Two modes of action 1. prevents binding (lowers affinity) 2. Abolishes activation of the receptor even after the agonist is bound

Kd

drug concentration required to bind 50% of the receptor sites in the system

Physiological Antagonist

when ligands bind to two separate receptors, they produce opposing physiological effects