1. The document discusses drug receptor interaction theories including occupation theory, rate theory, induced fit theory, macromolecular perturbation theory, activation-aggregation theory, and two-state receptor model. 2. It classifies ligands that bind to receptors as full agonists, partial agonists, or antagonists and describes different types of agonists and antagonists. 3. The key forces involved in drug-receptor binding are described as well as interactions that stabilize drug-receptor complexes such as ionic interactions, hydrogen bonding, and hydrophobic interactions.

1. AGONIST, ANTAGONIST
AND
THEORIES OF DRUG RECEPTOR
INTERACTION
PRESENTED BY
ABHISHEK GHARA
1st YEAR M. PHARM
DEPT. OF PHARMACEUTICAL CHEMISTRY

2. DRUG
It is a natural or synthetic substances which has a
physiological effects when administered into the body.
RECEPTOR
It is a specific binding site present on the cell surface
made up of protein or nucleic acid where a ligand can
bind and initiates a characteristic response.

3. CLASSIFICATION OF LIGANDS
Ligands are classified by effects upon binding to the
receptor
LIGAND
AGONIST ANTAGONIST

4. TYPES OF
AGONIST
FULL
AGONIST
Ligands that
increase the
activity of the
receptors &
produce the
maximal
response
PARTIAL
AGONIST
Ligands partially
increase the activity
of the receptors but
do not produce the
maximal response
like full agonist
even when present
in excess amount
INVERSE
AGONIST
Ligands which
decrease the
activity of an
active receptors
to their inactive
state

6. TYPES OF
ANTAGONIST
REVERSIBLE
COMPETITIVE
The antagonist
competes with the
agonist for the
orthosteric sites
for binding to the
same receptor .
NON
COMPETITIVE
The antagonist
binds at a different
site other than
orthosteric sites for
binding to the same
receptor .
IRREVERSIBLE
May or may not
competes with the
agonist for
orthosteric sites for
binding to the
receptor.

8. FORCES INVOLVED IN DRUG RECEPTOR
INTERACTION
Where kon is the rate constant for formation of the drug-receptor
complex, which depends on the concentration of the drug and the
receptor
koff is the rate constant for breakdown of the complex, which
depends on the concentration of the drug-receptor complex as well as
other forces.

9. The biological activity of drug is related to its affinity for the receptor,
i.e., the stability of the drug-receptor complex.
This stability is commonly measured by how difficult is for the complex
to dissociate, which is measured by its kd, the dissociation constant for
the drug-receptor complex at equilibrium.

10. INTERACTIONS INVOLVED IN THE DRUG-RECEPTOR
COMPLEX
1. Ionic interactions
2. Ion-dipole and dipole-dipole interactions,
3. Hydrogen bonding
4. Hydrophobic interactions
5. Vander waals interactions
6. Covalent bonding

11. 1. Occupation theory
2. Rate Theory
3. The induced-fit theory of enzyme-substrate interaction
4. Macromolecular perturbation theory
5. Activation-aggregation theory
6. Two state model of receptor activation
THEORIES OF DRUG RECEPTOR INTERACTIONS

12. OCCUPATION THEORY
Drugs act on binding sites and activate them, resulting in a biological
response that is proportional to the amount of drug-receptor complex
formed.
The response ceases when this complex dissociates.
Intensity of pharmacological effect is directly
proportional to number of receptors occupied
D + R  DR  RESPONSE
Response is proportional to the fraction of occupied receptors
Maximal response occurs when all the receptors are occupied

13. RATE THEORY
The response is proportional to the rate of drug-Receptor complex
formation.
Activation of receptors is proportional to the total number of encounters
of a drug with its receptor.
According to this view, the duration of Receptor occupation determines
whether a molecule is agonist, partial agonist.

14. THE INDUCED-FIT THEORY
According to this theory, binding produces a mutual plastic molding of
both the ligand and the receptor as a dynamic process.
The conformational change produced by the mutually induced fit in the
receptor macromolecule is then translated into the biological effect,
eliminating the rigid and obsolete “ lock and key” concept of earlier
times
Agonist induces conformational change – response
Antagonist does not induce conformational change – no response
Partial agonist induces partial conformational change-partial
response

15. MACROMOLECULAR PERTURBATION THEORY
Suggests that when a drug-receptor interaction occurs, one of two
general types of Macromolecular perturbation is possible:
a specific conformational perturbation leads to a biological response
(Agonist),
whereas a non specific conformational perturbation leads to no
biological response (Antagonist)

16. ACTIVATION AGGREGATION THEORY
Receptor is always in a state of dynamic equilibrium between activated
form (Ro) and inactive form (To).

17. TWO-STATE (MULTI-STATE) RECEPTOR MODEL
R and R* are in equilibrium (equilibrium
constant L), which defines the basal
activity of the receptor.
Full agonists bind only to R*
Partial agonists bind preferentially to R*
Full inverse agonists bind only to R
Partial inverse agonists bind
preferentially to R