about receptors, agonist and antagonist of receptor.

1. Prof. Dhanashri R. Mali
GES’s Sir Dr. M. S. Gosavi College of Pharmaceutical
Education and Research, Nashik.

2. Receptor is a protein molecule that is
embedded within the plasma membrane
and receives chemical signals from outside
the cell.
It recognises and responds to endogenous
chemical signals.
Ligand
cellmembrane with receptor
Biological responce

3. In pharmacology, It include other proteins
that are drug targets.
Eg: enzymes, transporters and ion channels.
Each receptor is linked to a specific cellular
biochemical pathway.
When a ligand binds to its corresponding
receptor, it activates or inhibits the receptor's
associated biochemical pathway.
A protein molecule, usually on the surface of
a cell, that is capable of binding to a
complementary molecule, as a hormone,
antibody or antigen.

4. History:
• In mid 1800 s, Claude Bernard, first
demonstrate this with experiment with
Curare.
• He postulate that Chemical Subs.
Communicate between Nerve and Target
Tissue.
• Today Known as “Chemical
Neurotransmission.”

5. • In Early 1900s, J. N. Langley, established
initial foundations for the interactions of
drugs with specific cellular components.
• He noted this with PILOCARPINE and
ATROPINE, both react with same
component of cell.
• Paul Ehrlich coined term RECEPTIVE
SUBSTANCE or RECEPTOR

6. Receptor diversity, their
complexicity in coupling to
regulatory proteins, signal
transduction pathways and
subsequent cellular events
reflects the root of variety of
diseases.

7. Ligands and receptors are in a dynamic relationship
R + L RL
Amount of RL depends on
• Concentration of L and R
• Affinity of R for L
All ligand molecules for a receptor can bind all
available receptors
Percentage of binding depends on:
•Concentration of each
•Affinity for each other

8. All ligands bind their receptor(s)
Ligands are classified by effect upon
binding to receptor
 Agonist if receptor changes
behavior
Ion channel opens
Receptor kinase is activated Etc.
 Antagonist if receptor does
nothing.

9. Agonists interact with receptors to produce the
same cellular effect that is seen with the naturally
occurring binding chemicals (ligands)
eg salbutamol (eg Ventolin) – agonist at beta2 receptors;
stimulation results in smooth muscle relaxation
Antagonists interact with receptors and block the
effects of the naturally occurring ligands
eg ranitidine (eg Zantac) – antagonist at histamine H2
receptors; blockade reduces acid secretion in the
stomach

11. Affinity:
Ability of Ligand to Bind Receptor
Efficacy(Intrinsic Activity):
Ability of ligand to elicit
pharmacoloigal response.

12. Agonist:
High Affinity and high Intrinsic activity.
Partial Agonist:
Affinity equal or less and less intrinsic
activity.
Antagonist:
high affinity and poor intrinsic activity.
Inverse agonist:
Opposite biological response.

13. Full agonist
“Drug with high efficacy enough to elicit a maximal tissue
response”
Partial agonist
“Drug with intermediate level of efficacy, such that even
when 100% of the receptors are occupied, the tissue
response is submaximal”

14.  Exhibits similar potency (EC50), but lower efficacy (emax)
 Produces concentration-effect curves that resemble those
observed with full agonists in the presence of an irreversible
antagonist
 Compared to full agonist can exhibit identical receptor
affinity (the blue curve)
 The failure of partial agonists to produce a maximal response
is not due to decreased receptor affinity  partial agonists
competitively inhibit the responses produced by full agonists
 Many clinical agents used as antagonists are actually partial
agonists
 For example, pindolol, a b-adrenoceptor "partial agonist,"
may act as either an agonist (if no full agonist is present) or
as an antagonist (if a full agonist such as isoproterenol is
present). Propranolol is devoid of agonist activity, i.e., it is a
pure antagonist

15.  A substance that does not provoke a
biological response itself, but blocks or
reduces agonist-mediated responses.
 Antagonists have affinity but no efficacy
for their cognate receptors
 Binding of antagonist to a receptor will
inhibit the function of a partial agonist,
an agonist or inverse agonist at that
receptor.
 Two types:
• Competitive
• Non- Competitive
Antagonist

16. Competitive Antagonist
 Binds to same site on receptor as agonist
 Two types:
Competitive reversible antagonist
Competitive Irreversible Antagonist
Competitive reversible antagonist
 inhibition can be overcome by increasing agonist concentration
(i.e., inhibition is reversible)
 No significant depression in maximal response
 Maximal response occurs at a higher agonist concentration
than in the absence of the antagonist
 It primarily affects agonist potency
 Clinically useful
 Example: Prazosin at a adrenergic receptors.

17. Competitive Irreversible Antagonist
 The antagonist possesses reactive group which forms covalent
bond with the receptor  the antagonist dissociates very slowly,
or not at all
 inhibition can not be overcome by increasing agonist
concentration
(i.e., inhibition is irreversible)
 Maximal response is depressed (i.e., Emax is decreased)
 Agonist potency may or may not be affected
 The only mechanism the body has for overcoming the block is to
synthesize new receptors
 Experimental tools for investigating receptor functions
 Example: phenoxybenzamine at a adrenergic receptors

18. Competitive antagonist

19. Non-competitive antagonist
 It does not bind to the same receptor sites as the agonist.
 It would either:
prevebind to a distinctly separate binding site from the agonist
decreased affinity of the receptor for the agonist, “allosteric
inhibition”,
nt conformational changes in the receptor required for receptor
activation after the agonist binds  “allosteric inhibition”,
or alternatively block at some point the chain of events that leads to
the production of a response by the agonist
Inhibition cannot be overcome by increasing agonist
concentration (irreversible)
Agonist maximal response will be depressed
 Agonist potency may or may not be affected
 Example: the noncompetitive antagonist action of crystal violet (CrV) on
nicotinic acetylcholine receptors.

20. Non-Competitive antagonist