Drug TargetsDrug[A]-Receptor[R] complex[AR] regulates cellular functionQuantum (All or None) ResponseTherapeutic IndexGraded Dose-Response CurveDrug TargetsKd = (Equilibrium) Dissociation constant (unit:M)fb[D]Kd + [D]= Low Kd = high affinity = difficult to dissociate, nM to pM High Kd = low affinity = quick to dissociate, mM to µMR + D RD Effectk1k2k3Kd = k2/k1 Dose-Response CurveOccupational Theory of Drug actionIn occupational theory of drug action, fraction of receptor binding is equal to the fraction of max effect.However, it was demonstrated later thatthe occupational theory does not work in most of cases.Response is not proportional to the fraction of receptor occupancy.1. Signal is amplified at the receptor.2. The concept of “spare receptors”.(100 % binding is not necessary to generate max response) Potency and Efficacy are independent.Agonist and Antagonist Antagonist: Competitive or NoncompetitiveCompetitive Antagonist and Noncompetitive antagonistPartial AgonistPotency and EfficacyInverse AgonistAllosteric Theory of Drug actionAllosteric Theory (two state theory) of drug actionResponse is not proportional to the fraction of receptor occupancy.1. Signal is amplified at the receptor.2. The concept of “spare receptors”.(100 % binding is not necessary to generate max response)Response is amplified at the
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