Most drugs must bind to a receptor to bring about an effect. However, at the molecular level, drug binding is only the first in what is often a complex sequence of steps.
Types of Drug-Receptor Interactions
Agonist drugs bind to and activate the receptor in some fashion, which directly or indirectly brings about the effect. Some receptors incorporate effector machinery in the same molecule, so that drug binding brings about the effect directly, eg, the opening of an ion channel or activation of enzyme activity. Other receptors are linked through one or more intervening coupling molecules to a separate effector molecule.
Pharmacologic antagonist drugs, by binding to a receptor, prevent binding by other molecules. For example, acetylcholine receptor blockers such as atropine are antagonists because they prevent access of acetylcholine and similar agonist drugs to the acetylcholine receptor and they stabilize the receptor in its inactive state. These
agents reduce the effects of acetylcholine and similar drugs in the body.
“Agonists” That Inhibit Their Binding Molecules and Partial Agonists.
Some drugs mimic agonist drugs by inhibiting the molecules responsible for terminating the action of an endogenous agonist. For example, acetylcholinesterase inhibitors, by slowing the destruction of endogenous acetylcholine, cause cholinomimetic effects that closely resemble the actions of cholinoceptor agonist molecules even though cholinesterase inhibitors do not—or only incidentally do—bind to cholinoceptors. Other drugs bind to receptors and activate them but do not evoke as great a response as so-called full agonists. Thus, pindolol, an adrenoceptor “partial agonist,” may act as either an agonist (if no full agonist is present) or as an antagonist (if a full agonist such as isoproterenol is present).
Duration of Drug Action
Termination of drug action at the receptor level results from one of several processes. In some cases, the effect lasts only as long as the drug occupies the receptor, so the dissociation of the drug from the receptor automatically terminates the effect. In many cases, however, the action may persist after the drug has dissociated, because, for example, some coupling molecule is still present in activated form. In the case of drugs that bind covalently to the receptor, the effect may persist until the drug-receptor complex is destroyed and new receptors are synthesized, as described previously for phenoxybenzamine. Finally, many receptor-effector systems incorporate desensitization mechanisms for preventing excessive activation when agonist molecules continue to be present for long periods.
Receptors and Inert Binding Sites
To function as a receptor, an endogenous molecule must first be selective in choosing ligands (drug molecules) to bind; and second, it must change its function upon binding in such a way that the function of the biological system (cell, tissue, etc) is altered. The first characteristic is required to avoid constant activation of the receptor by promiscuous binding of many different ligands. The second characteristic is clearly necessary if the ligand is to cause a pharmacologic effect. The body contains many molecules that are capable of binding drugs, however, and not all of these endogenous molecules are regulatory molecules. The binding of a drug to a nonregulatory molecule such as plasma albumin will result in no detectable change in the function of the biological system, so this endogenous molecule can be called an inert binding site. Such binding is not completely without significance, however, since it affects the distribution of drugs within the body and will determine the amount of free drugs in circulation. Both of these factors are of pharmacokinetic importance.
Reference: Bertram Katzung – Basic & Clinical Pharmacology.