Drug receptor targets

1. Lectures 2-3
Drug Targets
(Receptors)

2. DOSE
DRUG IN
TISSUES
DRUG IN
SYSTEMIC
CIRCULATION
EXCRETION
AND
METABOLISM
ABSORPTION
ELIMINATION
DISTRIBUTION
ADME

3. • Cell Membrane Lipids
• Proteins
• Receptors
• Enzymes
• Carrier proteins
• Structural proteins
• Nucleic acids
• DNA
• RNA
• Carbohydrates
• Cell surface carbohydrates
• Antigen and recognition molecules
Drug Targets
Konrad H. Bleicher, Hans-Joachim Böhm, Klaus Müller & Alexander I. Alanine
Nature Reviews Drug Discovery 2, 369-378 (May 2003)

4. Receptors

5. Drug-Receptor Interactions
1. Ionic (Electrostatic) Interactions

6. Drug-Receptor Interactions
Ion-Dipole and Dipole- Dipole Interactions

7. Drug-Receptor Interactions
Hydrogen Bonds

8. Drug-Receptor Interactions

9. Drug-Receptor Interactions

10. Drug-Receptor Interactions

11. Drug-Receptor Interactions
Charge-Transfer Hydrophobic Interactions

12. Drug-Receptor Interactions
π- π stacking Cation- π Interation

13. Drug-Receptor Interactions
Halogen Bonding

14. Drug-Receptor Interactions

15. Constitutive Receptor Activity

16. Drug-Receptor Interactions

17. Theories of Drug-Receptor Interactions
• Occupancy Theory
–The intensity of the body’s response to the drug is directly related to the number
of receptors occupied by the drug.
–The maximum response occurs when all of the receptors have drug molecules
attached.

18. Theories of Drug-Receptor Interactions
• Rate Theory
• Pharmacological response is not dependent on drug-receptor complex
concentration but rather depends upon rate of association of drug and receptor.

19. Drug-Receptor Interactions
• Two-state (Multi-state) Receptor Model
• R and R* are in equilibrium (equilibrium
constant L), which defines the basal activity of
the receptor.
• Full agonists bind only to R*
• Partial agonists bind preferentially to R*
• Full inverse agonists bind only to R
• Partial inverse agonists bind preferentially to R
• Antagonists have equal affinities for both R and
R* (no effect on basal activity)
• In the multi-state model there is more than one
R state to account for variable agonist and
inverse agonist behavior for the same receptor
type.

20. Drug Chirality

21. Conformational Isomers

22. Conformational Isomers

23. Diastereomers

24. Receptor Chirality
Roger A.H. Adan. Nature, Volume 27, Issue 4, 2006, 183–186

25. Topographical and Stereochemical
Considerations

26. Topographical and Stereochemical
Considerations

27. Allosteric Modulators