Transcript 2nd Lecture 1433

PHL 210
Pharmacology
Second Lecture
By
Abdelkader Ashour, Ph.D.
Phone: 4677212
Email: [email protected]
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 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
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
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
Drug
 In order to interact chemically with its receptor, a drug molecule must have
the appropriate size, electrical charge, shape, and atomic composition
 Orphan receptors
“Receptors for which no ligand has been discovered but they have a similar structure
to other identified receptors and whose function can only be presumed”
 If a ligand for an orphan receptor is later discovered, the receptor is referred to as "adopted
orphan receptor"
Drug Receptors,
contd.
 Receptor 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”
 Desensitization
“The loss of a drug’s effect, when it is given continuously or repeatedly, on a
short time-scale”
 Often results from receptor down-regulation
 Receptor 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 receptor up-regulation”
Drug Receptor Interactions
 Agonist
“A chemical messenger (or drug) 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 can bind to
muscarinic receptors but it does not trigger the cell’s response. In this way, it prevents
binding of acetylcholine (ACh) and similar agonist drugs to the ACh receptor
Drug Receptor Interactions
The Lock and Key Model of SignalReceptor Interaction
 Ligands such as hormones, neurotransmitters
or drugs (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
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