Transcript 351 Pharmacology 3rd sf

Pharmacology-1 PHL 351
Abdelkader Ashour, Ph.D.
Third Lecture
Drug Receptors
 Receptor/Binding site
“A specific protein in either the plasma membrane
or interior of a target cell with which a ligand/drug
combines”
 It must be selective in choosing ligands/drugs to
bind  To avoid constant activation of the receptor
by promiscuous binding of many different ligands
 It must change its function upon binding in such a
way that the function of the biologic system (cell,
tissue, etc) is altered  This is necessary for the
ligand to cause a pharmacologic effect
 Orphan receptors
“Receptors for which no ligand has been
discovered and whose function can only be
presumed”
Drug Receptors
 Receptor/Binding site
“A specific protein in either the plasma membrane
or interior of a target cell with which a ligand/drug
combines”
 It must be selective in choosing ligands/drugs to
bind  To avoid constant activation of the receptor
by promiscuous binding of many different ligands
 It must change its function upon binding in such a
way that the function of the biologic system (cell,
tissue, etc) is altered  This is necessary for the
ligand to cause a pharmacologic effect
 Orphan receptors
“Receptors for which no ligand has been
discovered and whose function can only be
presumed”
Drug Receptors
 Receptor/Binding site
“A specific protein in either the plasma membrane
or interior of a target cell with which a ligand/drug
combines”
 It must be selective in choosing ligands/drugs to
bind  To avoid constant activation of the receptor
by promiscuous binding of many different ligands
 It must change its function upon binding in such a
way that the function of the biologic system (cell,
tissue, etc) is altered  This is necessary for the
ligand to cause a pharmacologic effect
 Orphan receptors
“Receptors for which no ligand has been
discovered and whose function can only be
presumed”
 Specificity
“The ability of a receptor to bind only one type or a limited number of
structurally related types of ligands/drugs”
Drug Receptors,
contd.
 Down-regulation
“A decrease in the total number of target-cell receptors for a
given messenger/ligand in response to chronic high
extracellular concentration of the messenger/ligand”
 Up-regulation
“An increase in the total number of target-cell receptors for a given
messenger/ligand in response to a chronic low extracellular concentration of
the messenger/ligand”
 Supersensitivity
“The increased responsiveness of a target cell to a given messenger/ligand,
resulting from up-regulation”
Drug Receptor Interactions
The Lock and Key Model of Signal-Receptor
Interaction
 Ligands such as hormones or neurotransmitters (the"key")
affect target cells by binding to specific receptors (the
"lock”), which are often located in the cell membrane
 This binding "unlocks" the cell's response, so that the
hormone or neurotransmitter can exert its effects
 Agonist
“A chemical messenger that binds to a receptor and triggers the cell’s response;
often refers to a drug that mimics a normal messenger’s action”.
 For example, pilocarpine is a muscarinic receptor agonist because it can bind to and
activate muscarinic receptors
 Antagonist
"A molecule that competes for a receptor with a chemical messenger normally
present in the body. The antagonist binds to the receptor but does not trigger
the cell’s response”
 For Example, atropine is a muscarinic receptor antagonist because it prevents
access of acetylcholine and similar agonist drugs to the acetylcholine receptor
Drug Receptor Interactions
Lock and key mechanism
Agonist
Receptor
Agonist-Receptor
Interaction
Drug Receptor Interactions
Competitive
Inhibition
Antagonist
Receptor
DENIED!
Antagonist-Receptor
Complex
Drug Receptor Interactions
Non-competitive
Inhibition
Agonist
Antagonist
Receptor
DENIED!
‘Inhibited’-Receptor
Drug Receptor Interactions, contd.
 Affinity
The extent to which the ligand/drug is capable of binding and remained
bound to receptor.
 High Affinity – the ligand binds well and remains bound long enough to activate
the receptor.
 Low Affinity – the ligand binds less well and may not remain bound long enough
to activate the receptor.
High Affinity
Drug Receptor Interactions, contd.
 Affinity
The extent to which the ligand/drug is capable of binding and remained
bound to receptor.
 High Affinity – the ligand binds well and remains bound long enough to activate
the receptor
 Low Affinity – the ligand binds less well and may not remain bound long enough
to activate the receptor
Low Affinity
Dose-Response Functions
Biological Effect
Displays the relationship between the dose of a ligand and some
biological response to that ligand
Dose-Response Functions, contd.
 Efficacy (Emax)
The maximal response that the drug can produce. It is the effect that is
observed at saturating concentrations
 Agonists will have high efficacy, whereas antagonists will, generally, have zero efficacy
 EC50/ED50
The concentration or dose of the drug that is needed to produce a 50%
maximal response
(A)
Red
(B)
Which drug has more efficacy? And why?
Dose-Response Functions, contd.
 Potency
The amount (weight) of drug in relation to its effect.
For example, if the weight-for-weight drug A has a greater effect than drug B 
drug A is more potent than drug B, although the maximum therapeutic effect may
be similar with both drugs
 Drugs of high potency will generally have a high affinity for the receptors and
thus occupy a significant proportion of the receptors even at low
concentrations
Dose-Response Functions, contd.
Biological Effect
Efficacy & Potency
A
B
Which drug has more efficacy? Which drug has more potency? And
why?
Efficacy: A=B
Potency: A>B
Dose-Response Functions, contd.
Biological Effect
Efficacy & Potency
A
B
Which drug has more efficacy? Which drug has more potency? And
why?
Efficacy: A>B
Potency: A=B
Dose-Response Functions, contd.
Biological Effect
Efficacy & Potency
A
B
Which drug has more efficacy? Which drug has more potency? And
why?
Efficacy: A>B
Potency: A>B