Drug Targets Drug A Receptor R complex AR regulates cellular function Quantum All or None Response Therapeutic Index Graded Dose Response Curve Drug Targets Broadly defined as any target molecule with which a drug molecule combine and elicit specific effect Same applies to a physiological ligand A more specific pharmacological definition applies to a macromolecule that serves as a recognition site for a chemical agent ligand and mediates the action of the ligand Many receptors are expressed on cell surface but some are present inside the cell e g nuclear receptors For a molecule to qualify as a receptor it must meet 3 criteria 1 In a given sample there is finite number of receptors saturation of binding and effect 2 Ligand binding is specific and can be competed off by a ligand of the same or similar structure e g agonists and antagonists 3 Binding kinetics is consistent with biological effect concentration and time dependency Kd Equilibrium Dissociation constant unit M Kd k2 k1 R D k 1 RD k 3 Effect k2 Low Kd high affinity difficult to dissociate nM to pM High Kd low affinity quick to dissociate mM to M fb D Kd D Dose Response Curve Occupational Theory of Drug action In occupational theory of drug action fraction of receptor binding is equal to the fraction of max effect However it was demonstrated later that the occupational theory does not work in most of cases Response is not proportional to the fraction of receptor occupancy 100 binding is not necessary to generate max response 1 2 Signal is amplified at the receptor The concept of spare receptors Potency and Efficacy Potency and Efficacy are independent Agonist and Antagonist Antagonist Competitive or Noncompetitive Partial Agonist Question Draw a dose response curve of a partial agonist in the presence of a fixed amount of full agonist Allosteric Theory of Drug action Inverse Agonist Allosteric Theory two state theory of drug action Response is amplified at the membrane
View Full Document
Unlocking...