Drugs & Behavior 65.2   Basic Principles of PsychopharmacologyPharmacodynamics: Drug-Receptor Interactions
Pharmacodynamics (PD)• Pharmacodynamics: biochemical &  physiological effects of drugs and their  mechanisms of action• Dr...
PD: Drugs & Receptors• Receptor: large molecules of protein where ligands induce  effects• Ligands: endogenous; biological...
Ionotropic & Metabotropic Receptors
PD: Law of Mass Action D + R ←→DR*→biological effect                      Active                    Complex     CellularDr...
PD: Law of Mass Action   D + R ←→DR*→biological effect•The active form DR* is in equilibrium with the inactivecomponents D...
PD: Law of Mass Action & DRC                                      Max ResponseResponse is in proportion to fraction of rec...
PD: Drugs & Receptors• Full Agonists: affinity and efficacy; facilitates  or increases neural transmission     D + R ←→ DR...
PD: Drugs & Receptors• Types of Agonists  – Direct Agonist: exerts effect at receptor site  – Indirect Agonist: does not b...
GABAa receptorInverse Agonist:Causes                                            Indirect Antagonist                      D...
PD: Drugs & Receptors• Types of Antagonists  – Competitive Antagonists: affinity without efficacy;    competition for fixe...
PD: Drugs & Receptors• Types of Antagonists  – Non-competitive antagonists: high affinity without    efficacy; AR complex ...
NMDA receptorDirect Agonist                                      Direct Agonist                                 Non-compet...
PD: Drugs & Receptors• Other D-R Interactions  – Mixed Agonist-Antagonist: drug will act as an agonist at    receptor A bu...
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Drugs & behavior_pd_7

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  • When receptor number held constant, and we increase the concentration of the drug, we form greater amounts of DR complexes and attain greater effects. Maximum effect is achieved when receptors are fully occupied.
  • When receptor number held constant, and we increase the concentration of the drug, we form greater amounts of DR complexes and attain greater effects. Maximum effect is achieved when receptors are fully occupied.
  • Drugs & behavior_pd_7

    1. 1. Drugs & Behavior 65.2 Basic Principles of PsychopharmacologyPharmacodynamics: Drug-Receptor Interactions
    2. 2. Pharmacodynamics (PD)• Pharmacodynamics: biochemical & physiological effects of drugs and their mechanisms of action• Drug binding – Law of Mass Action • Depot Binding (covered in PK lecture) • Drug-Receptor Coupling • DRC Revisited (covered in basics lecture)
    3. 3. PD: Drugs & Receptors• Receptor: large molecules of protein where ligands induce effects• Ligands: endogenous; biologically active chemicals such as hormones, neurotransmitters, neuromodulators, neurohormones• Drug: exogenous• Receptor + Ligand/Drug Coupling (Lock & Key Analogy)• Affinity: relative capacity of a compound to maintain contact with or be bound to a receptor• Efficacy: degree of biological activity or relative capability of a compound to activate the receptor after being bound to it
    4. 4. Ionotropic & Metabotropic Receptors
    5. 5. PD: Law of Mass Action D + R ←→DR*→biological effect Active Complex CellularDrug Reversible Behavioral Receptor Response
    6. 6. PD: Law of Mass Action D + R ←→DR*→biological effect•The active form DR* is in equilibrium with the inactivecomponents D,R •Drug associated with receptor and then dissociates; weaker non-covalent interactions 1) Ionic or electrostatic: bond formed between charged groups on receptor 2) Hydrogen bonds: exchange of hydrogen bond between drug molecule, receptor, and surrounding environment 3) Hydrophobic Interactions: non-polar hydrocarbon groups on receptor and drug molecule; non-specific bonds
    7. 7. PD: Law of Mass Action & DRC Max ResponseResponse is in proportion to fraction of receptors occupied!
    8. 8. PD: Drugs & Receptors• Full Agonists: affinity and efficacy; facilitates or increases neural transmission D + R ←→ DR* →biological effect• Antagonist: affinity without efficacy; drug binds to receptor but fails to initiate intracellular effect; blocks agonist A + R ←→ AR → no biological effect
    9. 9. PD: Drugs & Receptors• Types of Agonists – Direct Agonist: exerts effect at receptor site – Indirect Agonist: does not bind directly with receptor but enhances amount of endogenous ligand available – Partial Agonist: Intermediate efficacy in receptor activation; may have greater affinity than full agonist; Abilify @ DA receptors is good example. – Inverse Agonist: drug acts through same receptor as agonist but produces effects opposite to those of an agonist (negative efficacy); BZD example.
    10. 10. GABAa receptorInverse Agonist:Causes Indirect Antagonist Direct Agonists: muscimolconvulsions BDZs Valium, Xanax are Indirect AgonistsIndirect Agonists BUT!!!PhenobarbitolPentobarbitol Endogenous substance is Inverse AgonistDirect Antagonists:bicuculine
    11. 11. PD: Drugs & Receptors• Types of Antagonists – Competitive Antagonists: affinity without efficacy; competition for fixed number of receptors affected by concentration D + A + R ←→ DR* + AR D α DR* D+A DR* + AR
    12. 12. PD: Drugs & Receptors• Types of Antagonists – Non-competitive antagonists: high affinity without efficacy; AR complex not affected by concentration A + R ←→ AR → no biological effect A + R → AR → no biological effect – NMDA receptor & PCP – Different sites along neural pathway – Reversible and irreversible
    13. 13. NMDA receptorDirect Agonist Direct Agonist Non-competitive antagonist
    14. 14. PD: Drugs & Receptors• Other D-R Interactions – Mixed Agonist-Antagonist: drug will act as an agonist at receptor A but as an antagonist at receptor B • When administered alone, will facilitate neurotransmitter function at one receptor but block neurotransmitter function at the other – Ex: GABAa and GABAa receptor subunits • When combined with a full agonist that activates both receptors (A, B), the mixed agonist-antagonist blocks some of the effects of full agonist – EX: GABAa and GABAb receptor both activated by GABA – Mixed agonist-antagonist will block some effects of GABA at the GABAb receptor but not the GABAa receptor – Our drug is then an agonist at GABAa and an antagonist at GABAb

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