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.
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
18.
19. SPARE RECEPTOR
Spare receptor also known as a “reserve receptor” or
“efficacy reserve” , refers to a phenomenon in
pharmacology where a maximal response can be
achieved with only a fraction of the total available
receptors being occupied by a drug or ligand.
Spare receptors are receptors that remain unbound
when an agonist is producing its maximal biologic
response
20. SPARE RECEPTOR CONT…
to determine the presence of spare receptors ,
scientists often compare the concentration of drug
needed to produce 50% of the maximum
effect(ec50) with the concentration of drug needed to
occupy 50% of receptors(kd).
Spare receptors act as functional reserves and
allows cells to economically use endogenous
agonists such as hormones and neurotransmitters.
The concept of spare receptors has important
implications for drug development and efficacy.
21. SPARE RECEPTOR CONT…
It suggests that drugs targeting receptors with spare
capacity can still produce a full response even at lower
concentrations or with partial receptor occupancy.
The existence of spare receptors also highlights the
complexity of drug-receptor interactions and the
potential for multiple signaling pathways to be activated
or modulated.
The spare receptors may play a role in maintaining
receptor sensitivity and responsiveness in certain
physiological or pathological conditions.
Overall, spare receptors provide a valuable concept in
understanding drug-receptor interactions and have
implications for drug design, dosing, and therapeutic
efficacy.
