Drug Targets

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Drug Targets
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DrugA-ReceptorR complexAR regulates
cellular function
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Quantum (All or None) Response
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Therapeutic Index
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Graded Dose-Response Curve
Hyperbolic curve
Sigmoidal Curve
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Drug Targets
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Kd (Equilibrium) Dissociation constant (unitM)
Low Kd high affinity difficult to
dissociate, nM to pM High Kd low
affinity quick to dissociate, mM to ?M
fb fractional binding of receptor
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Dose-Response Curve Occupational Theory of
Drug action
However, it was demonstrated later that the
occupational theory does not work in most of
cases.
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Response is not proportional to the fraction of
receptor occupancy.
(100 binding is not necessary to generate max
response)
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Potency and Efficacy are independent.
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Agonist and Antagonist
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Antagonist Competitive or Noncompetitive
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Partial Agonist
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Inverse Agonist
Allosteric Theory of Drug action
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Allosteric Theory (two state theory) of drug
action
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Signal transduction pathways in mammalian cells
Pharmacological basis of therapeutics 10th
edition by Goodman Gilman
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Four types of receptor
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Four types of receptor
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Classification of G? subunits
Gs Gs? Adenylyl Cyclase (stimutation) Golf?
Gi Gt?? cGMP Phosphodiesterase
(stimulation) Gt?? Gi?? Adenylyl Cyclase
(inhibition) Gi?? Gi?? Go?A Adenylyl Cyclase
(inhibition) (?) Go?B Gz? Adenylyl
Cyclase (inhibition)
Gq Gq? Phospholipase C ???stimulation) G11?
G14? G15/16? G12 G12? RhoGEF
(stimulation) G13?
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Soluble second messengers
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Desensitization of Receptor-mediated response
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Desensitization of G protein-mediated signaling
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