FFP1 - Agonists

Overview of Agonists

Definitions

  • Ligands: Chemicals that specifically bind to receptors.

  • Receptors: Proteins that bind ligands, initiating a biological response.

  • Agonists: Ligands that bind to receptors resulting in a biological response.

  • Antagonists: Ligands that bind to receptors but do not produce a biological response; they also prevent other ligands from binding


Receptor-Ligand Interactions

  • Receptors show high affinity for their endogenous ligands at physiological concentrations.

  • Characteristics of receptors:

    • Saturable: They have a limited number of binding sites.

    • Finite: Only a certain amount of ligand can bind to them.

Specific Binding of Ligands

  • Receptor structure enables recognition of specific ligands.

  • A single receptor type can interact with various ligands, leading to different signalling outcomes.

  • Different tissues can express the same receptor, mediating distinct physiological responses.

Dose-Response Relationship

  • The fraction of occupied receptors is directly proportional to the physiological response.

Key Concepts in Dose-Response Curves

  • EC50: The concentration of an agonist that produces 50% of the maximum response.

  • Potency: The amount of drug needed to produce a given effect; relates to affinity for the receptor.

  • Bmax: Maximum binding of a drug to a receptor.

  • Kd (Dissociation constant): Concentration at which half of the available receptors are bound.

Types of Agonists

Full Agonists

  • Activate receptors to elicit a full biological response. Either ON or OFF (e.g., codeine, fentanyl).

Partial Agonists

  • Bind to receptors, but induce a reduced signaling response compared to full agonists.

  • Their intrinsic activity (efficacy) is greater than 0 but less than 1, producing a dose-dependent response that never reaches maximum output.

  • Examples:

    • Buprenorphine - A partial agonist at mu-opioid receptors used in pain management.

    • Nicotinic Partial Agonists - Used in nicotine replacement therapy, easing withdrawal symptoms by activating nicotinic receptors while preventing full activation.

Spare Receptors

  • Maximum signalling responses can occur without full occupancy of all available receptors.

Measuring Receptor Activity

  • Various methods exist to assess how drugs interact with receptors:

    • Functional studies measure tissue response to drugs.

    • Binding studies measure the binding affinity of drugs to specific receptors.