Terms related to drug - receptor binding

INTRODUCTION TO TERMS

Agonists

  • Agonists are agents that mimic the effects of the endogenous regulatory compound.
  • Agonists may be defined as drugs that possess affinity for a particular kind of a receptor and has the ability to cause a change in the receptor that gives rise to an observable effect. Their value in clinical practice often rests on their greater capacity to resist degeneration and thus acts for a longer duration than the natural substances they mimic. For this reason, bronchodilatation produced by salbutamol lasts longer than that induced by adrenaline.
  • The properties exhibited by agonists include affinity, intrinsic activity, maximal efficacy, potency, selectivity and specificity.
  • Affinity of a ligand (drug or endogenous substance) is a measure of its capacity to bind to the receptor. Affinity may vary greatly among agonists as well as antagonists. Intrinsic activity is a measure of the ability of the agonist-receptor complex to initiate the observed biological response. A full agonist has an intrinsic activity of 1.
  • Maximal efficacy reflects the upper limit of the dose-response relationship without toxic effects being evident. Agonists differ from each other in this regard.
  • Potency refers to the range of concentrations over which an agonist produces increasing responses. Highly potent drugs produce their effects at lower concentrations; this may impart an advantage to their clinical use, provided the increase in potency is not accompanied by an increase in toxicity.
  • Agonists in their occupation of receptors exhibit selectivity and specificity. Few agonists are so specific that they interact only with a single subtype of receptor. However, several agonists do show evidences of selectivity for certain subpopulation of receptors.

Full agonists

  • Full agonists are agonists that produce a maximal response by occupying all or a fraction of receptors.

Partial agonists

  • Partial agonists are drugs that act both as agonists and antagonists. These drugs in addition to blocking access of the natural agonist to the receptor are capable of a low degree of activation. These agents produce less than a maximal response even when they occupy all of the receptors.
  • Inverse agonists Some substances produce effects that are specifically opposite to those of agonists and are called as inverse agonists.

Antagonists

  • These are agents that are themselves devoid of any intrinsic activity but cause the effects by inhibition of the action of an agonist. Drugs that have no activating effect whatsoever on the receptor are termed as pure antagonists.
  • They are sufficiently similar to the natural agonist to be ‘recognized’ by the receptor and to occupy without activating it, thereby preventing the natural agonist from exerting its effect.

Down regulation

  • When tissues are continuously exposed to an agonist, the number of receptors decreases and this may lead to a reduction in the number of receptors. This may be a reason for tachyphylaxis.

Up regulation

  • Prolonged contact with an antagonist leads to formation of new receptors and this phenomenon is known as up regulation.

Spare receptors

  • This term refers to the production of a maximal tissue response when only a fraction of the total number of receptors is occupied.

EC50: The concentration of an agonist that produces half maximal effect is known as EC50.

IC50: The concentration of an antagonist that produces half maximal inhibition is known as IC50.
Last modified: Wednesday, 25 April 2012, 7:03 AM