1. Drugs & Behavior 65.2
Basic Principles of Psychopharmacology
Pharmacodynamics: Drug-Receptor Interactions

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. 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. Ionotropic & Metabotropic Receptors

5. PD: Law of Mass Action
D + R ←→DR*→biological effect
Active
Complex Cellular
Drug Reversible Behavioral
Receptor Response

6. PD: Law of Mass Action
D + R ←→DR*→biological effect
•The active form DR* is in equilibrium with the inactive
components 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. PD: Law of Mass Action & DRC
Max Response
Response is in proportion to fraction of receptors occupied!

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. 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. GABAa receptor
Inverse Agonist:
Causes Indirect Antagonist
Direct Agonists: muscimol
convulsions
BDZs Valium, Xanax
are Indirect Agonists
Indirect Agonists BUT!!!
Phenobarbitol
Pentobarbitol Endogenous
substance is Inverse
Agonist
Direct Antagonists:
bicuculine

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. 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. NMDA receptor
Direct Agonist
Direct Agonist
Non-competitive
antagonist

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