Drug Action at Receptors

1
Drug Action at Receptors

• What are receptors? How do they work?
• Drug action at receptors

2
Part II Drugs and receptors

• Receptors are a major target for drugs
• Faulty communication between nerves and cells can
  lead to disease/ailments
• Drugs
• Agonists
• Antagonists

3
Agonists

• Receptor binding site
• Design of agonist
• Correct binding groups
• Correctly positioned
• Correct size

4
Enantiomers

• Asymmetrical Synthesis

5
Pharmacophore
6
Antagonists
7
Other types of antagonists

• Allosteric antagonists
• Antagonism by the umbrella effect

8
Partial agonists

• Small conformational change
• Multiple binding, same receptor
• Multiple receptors (see Table 5.1)

9
Equilibrium between active and inactive receptor
conformations
10
Identifying the pharmacophore

• Oxamniquine is an important Third World drug used
  in the treatment of schistosomiasis (bilharzia).
  Consider the structures below of oxamniquine (A)
  and two of the additional drugs tested in the
  design of oxamniquine. Based on these structures,
  draw the pharmacophore of oxamniquine.

11
Designing drugs

• The structure of epinephrine is shown below.
• Based on this structure, predict the binding site
  of an adrenergic receptor
• Design an agonist for your receptor
• Design an antagonist for your receptor

12
Question

• What happens when a drug binds to the receptor
  and stays for a prolonged period of time?
• Desensitization
• Sensitization

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1. Desensitization

• Phosphorylation
• Endocytosis
• Reduction of receptors

14
2. Sensitization

• Prolonged deactivation by antagonist leads to
  deficiency of messages sent to cell
• Leads to tolerance and dependence

15
Cytoplasmic receptors
16
An anticancer agent

• Tamoxifen (Nolvadex)

• Aminoglutethimide (Orimeten, Cytadren)