What is a Receptor?

• Definition: A receptor is a protein molecule that specifically recognises and binds to a small molecule called a ligand, leading to a series of biochemical events that result in a physiological response.

Drug-Receptor Binding

• Lock and Key Model: The drug (key) must fit into the receptor (lock) based on the correct size, shape, and chemical properties.
• Affinity: The strength of the interaction between a drug and its receptor.
  • High affinity leads to strong binding and is often associated with potent drugs.
  • Affinity is quantified by the equilibrium dissociation constant (KD), which represents the concentration needed to occupy half of the receptors. A lower KD indicates higher affinity.

Types of Drug-Receptor Interactions and Effects

1. Agonists:

   • Full Agonists: Produce the maximal biological response.
   • Partial Agonists: Elicit only a submaximal response, even at full receptor occupancy. They can act as antagonists in the presence of full agonists by competing for binding sites.

2. Antagonists:

   • Competitive Antagonists: Bind reversibly to the same site as the agonist. Their effects can be overcome by increasing the agonist concentration.
   • Non-competitive Antagonists: Bind to a different site or bind irreversibly, altering receptor function or blocking agonist binding. Their effects cannot be overcome by increasing agonist concentration.

3. Inverse Agonists: Bind to receptors with constitutive activity (active without a ligand) and decrease their activity.

4. Mixed Agonists-Antagonists: Exhibit agonist activity at some receptor subtypes and antagonist activity at others.

Dose-Response Relationships

• Graded Dose-Response Curves: Illustrate the relationship between drug concentration and response magnitude.

  • Potency: Amount of drug needed to produce an effect, often measured by EC50 (concentration producing 50% of maximum effect). A lower EC50 indicates higher potency.
  • Efficacy: The maximum effect a drug can achieve.

• Quantal Dose-Response Curves: Show the relationship between drug dose and the proportion of the population experiencing a specific effect.

  • ED50: Dose at which 50% of the population shows the desired effect.
  • TD50: Dose at which 50% of the population experiences a toxic effect.
  • Therapeutic Index (TI): TD50/ED50 ratio representing the drug’s safety margin. A larger TI indicates a safer drug.

Factors Influencing Drug-Receptor Interactions

• Drug Factors:
  • Size, shape, and chemical properties.
  • Types of binding interactions (e.g., Van der Waals forces, hydrogen bonds, covalent bonds).
• Receptor Factors:
  • Receptor subtypes and their distribution influence drug selectivity.
• Cellular Factors:
  • Downregulation: Decreased receptor numbers with chronic agonist exposure, leading to desensitisation.
  • Upregulation: Increased receptor numbers with chronic antagonist exposure, leading to supersensitivity.

Signalling Mechanisms

• Drug-receptor binding initiates a cascade of intracellular events, which can involve:
  • Ion channels.
  • Enzymes.
  • Second messengers (e.g., cAMP, IP3).
  • Protein kinases.
  • Gene expression (e.g., steroid hormones).

Importance of Drug-Receptor Interactions

• Drug Development: Understanding receptor interactions is critical for designing drugs that target specific receptors for therapeutic purposes.
• Clinical Practice: Knowledge of these interactions informs prescribing decisions, predicts drug effects, and manages drug interactions and adverse effects.

References

1. MSD Manual. (n.d.). Drug–Receptor Interactions. Retrieved from MSD Manual.
2. Berridge, M. J. (2018). The interaction between drugs and receptors. Journal of Pharmacology and Toxicology, 12(1), 45-60. Retrieved from ScienceDirect.
3. ScienceDirect. (n.d.). Drug-Receptor Interactions. Retrieved from ScienceDirect.
4. Open Access Journals. (n.d.). Understanding Drug-Receptor Interactions: Unlocking the Secrets of Pharmaceutical Action. Retrieved from Open Access Journals.