药理学Chapter2：药效学.ppt

Fig. 2-7 The two-state model. The receptor is shown in two conformational states, resting (R) and activated R*, which exist in equilibrium. 占领学说Occupation theory D + R DR E K1 K2 When receptors are occupied, the pharmacological effects will occur. The effects of drug are directly proportional to the numbers of receptors occupied. 占领学说的发展Development of occupation theory Clark（1926） D + R DR E K1 K2 令 KD = K2 / K1； 占领学说的发展Development of occupation theory 因为: [RT]=[R]+[DR]，[R]=[RT]-[DR]； 代入R得： 整理后得：[DR](KD+[D])=[D] [RT] 占领学说的发展Development of occupation theory When [DR]/[RT]=0, E=0. When [D]＞＞KD, [DR]/[RT]=1, [DR]=[RT] , E=Emax. When [DR]/[RT]=1/2, E=50%Emax, KD = [D]. 药物与受体的相互作用Interaction between drug and receptor KD = [D] pD2 (affinity index) 占领学说的发展Development of occupation theory pD2→affinity index (亲和力指数) Ariens(1954)：?→intrinsic activity (内在活性) ( 0?1) Stephenson(1956)：spare receptor (储备受体) silent receptor (沉默受体) .. 占领学说的发展Development of occupation theory When pD2 of drug A is the same as that of drug B, effect of drug is decided by ? . When ? of drug A is the same as that of drug B, effect of drug is decided by pD2. Affinity index (pD2) : A=B=C intrinsic activity (?): ABC Affinity index (pD2) : X＞Y＞Z intrinsic activity (?): X=Y=Z 药物的分类Classification of the drug Drug can be divided into different group according to the receptor theory: 激动剂 Agonist 纯激动剂 Absolute agonist 部分激动剂 Partial agonist 反向激动剂 Inverse agonists Partial agonist can evoke weak agonist effects but may also displace full agonists from the binding sites and reduce their biologic effect. 药物的分类Classification of the drug 拮抗剂 Antagonist 可逆性竞争性拮抗剂 Reversible competitive antagonist pA2=-log(I)2 不可逆性竞争性拮抗剂 Irreversible competitive antagonist pA’2= -log(I’)2 Antagonist binds to a receptor without producing any of the effects associated with agonist binding. 可逆性竞争性拮