receptor theories

1. DRUG RECPTOR INTERACTION
THEORY AND SPARE RECPTOR

2. OBJECTIVE
 Upon studying onto the Topic, students will
 Define what drug interaction theories explain
 Understand what govers drug-receptor interaction
 List 5 types of drug-receptor interaction theorys
 Define and explain the theories and list their
limitation
 Define what spare recptor is

3. Drug receptor interaction theories
 Drug receptor interaction theories explain how
drugs interact with receptors to produce a
physiological response.
 The interaction between the drug and receptor is
governed by the law of mass action; The rate at
which new drug to receptor complexes are
formed is proportional to the concentration of
drug.

4. THEORIES OF DRUG RECEPTOR
INTERACTIONS
THEORIES OF DRUG RECEPTOR INTERACTIONS
1, OCCUPATION THEORY
2, RATE THEORY
3, ALLOSTERIC THEORY
4,LOCK AN KEY THEORY
5, INDUCED-FIT THEORY

5. THEORIES OF DRUG RECEPTOR
INTERA…
1, OCCUPATION THEORY
 Developed by British pharmacologist A.J.Clark
 “States that activation of membrane receptors and target
cell response is proportional to the degree of receptor
occupancy”
 Assumed that the magnitude of the response is directly
proportional to the amount of drug bound
 Maximal effect occurs when all receptors are occupied.

6. Occupational THIORY CONT…


7. OCCUPATIONAL THIORY CONT…
 This theory suggest that the response to drugs
depends on
 the proportion of receptors occupied by drugs
(an active agonist is not always necessarily
needed to have maximal response)
 The drug affinity to the receptor (the ability of the
drug to bind to the receptor)
 The drugs intrinsic activity (the ability of the drug
to activate the receptor

8. OCCUPATION THEORY CONT…
 Limitation of occupation theory
 Some drugs acting at the same receptor can elicit
different maximal effect at maximal receptor
occupancy
 Some agonist never elicit a maximal response even
when nearly all the receptor are occupied

9. 2.RATE THEORY
RATE THEORY
 Developed by the American pharmacologist Louis S.
Goodman in 1953
 States “the effect of drug is depends on the rate of
binding of the drugs with the receptor
 Activation of receptor is proportional to the total
numbers of encounters of a drug with its receptor per
unit time `
 According to this view, the duration of receptor
occupation determines whether a molecules agonist,
partial agonist of antagonist.

10. RATE THEORY CONT…
 In the case of agonist, the rate of both association
and dissociation would be fast
 The rate of association of an antagonist with a
receptor would be fast but the dissociation would be
slow
 Partial agonist would have intermediate drug
receptor complex dissociation rates
 LIMITATION: It does not rationalize why different
types of compounds exhibit the characteristics they
do

11. 3. ALLOSTERIC THEORY
 Allosteric theory
 Developed by sir James black, a Scottish
pharmacologist and Nobel prize winner.
 Propose that drugs can bind to a receptor at a site
distinct from the active site, known as allosteric site.
This binding can enhance or inhibit the activity of
receptor
 Allosteric modulator can increase the affinity of
receptor for its endogenous ligand, leading to
increased receptor activation and a stronger response.
On the other hand negative allosteric modulator
decrease the affinity of the receptor for its ligand,
resulting in decreased receptor activation and a
weaker response

12. ALLOSTERIC THEORY CONT…
 The allosteric theory provides a more nuanced
understanding of drug receptor interaction and offers
potential opportunities for drug development. By
targeting allosteric sites, researchers can design
drugs that selectively modulate receptor activity,
leading to more precise and tailored therapeutic
effects additionally, allosteric modulators may offer
advantages over traditional orthostatic ligand, as
they can provide greater selectivity and reduce the
risk of off-target effects

13. ALLOSTERIC THEORY CONT…
LIMITATION
 it can be challenging to identify and target allosteric
sites.
 another limitation is that allosteric modulator can
have complex and unpredictable effects on receptor
activity.
 the allosteric theory may not fully explain all drug
receptor interaction.

14. 4,LOCK AND KEY THEORY
 The lock and key theory is a simplified analogy used
to explain drug-receptor interactions.
 According to this theory, the drug molecule (the key)
and the receptor molecule(the lock) have
complementary shapes and together like a key fits
into a lock.
 The lock and key theory also suggests that only
certain drugs can bind to a specific receptor, just as
only specific key can open a particular lock. This is
due to the unique shape and chemical properties of
both the drug and receptor.

15. LOCK AND KEY THEORY CONT…
 Limitation:-It does not fully account for the dynamic
nature of drug-receptor interactions.
-It does not explain the phenomena of
promiscuity, where a drug can bind to multiple
receptors with varying affinities.
-It does not consider allosteric modulation.

16. 5. INDUCED-FIT THEORIES
 States that the morphology of the binding sites is not
necessarily complementary with even the preferred
conformation of the ligand.
 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 mutual
induced-fit in the receptor macromolecule is then
translated in to the biological effect, eliminating the
rigid and obsolete “ key and lock” concept of
earlier times.

17. INDUCED-FIT THEORY CONT…
 Agonist induces conformational changes-response.
 Antagonist does not induce conformational change-
no response.
 Partial agonist induces partial conformational
change-partial response.
 Limitation:- Lack of specificity
-Incomplete explanation of drug efficacy
-Lack of consideration for allosteric
modulation
-Over emphasis on protein structure