Explain the concept of drug action with respect to receptor theory, enzyme interactions and physicochemical interactions. Receptor theory and its role in drug therapy article. The receptor theory assumes that all receptors should be occupied to produce a maximal response. A drug that activates a receptor is called an agonist. Specific areas of cell membranes proteins, glycoproteins. Receptor theory is the application of receptor models to explain drug behavior. Occupancy theory rests on the concept that the proportion of occupied receptors is related to the effect of the drug eg. Receptor theory of drug action deranged physiology.
The receptor theory is as important and basic to pharmacology as the atomic theory is to physical sciences. People also differ in pharmacodynamics, for example the number of drug receptors they have or their physiological response to a particular concentration of drug at the site of action. Balis, in principles of clinical pharmacology second edition, 2007. Rate theory the response is proportional to the rate of drug receptor complex formation. Induced fit model for more than 100 years, the behaviour of enzymes had been explained by the. Receptor based drug design 1 structurebased drug design or direct drug design relies on. Thus, the operational model has supplanted anal ysis of drugreceptor interaction in functional systems whereas the extended ternary complex model is used.
A drug molecule is considerably smaller in size than a receptor. The agonist does not get modified, or changed, by interaction with the receptor receptor theory 101 enzyme kinetics. Experiments with isolated tissues have been crucial in defining interactions between drugs and receptors, and in formulating drug receptor theory. Ppt receptor theory powerpoint presentation free to view. All books are in clear copy here, and all files are secure so dont worry about it.
Receptor for many hormones and slow transmitters 3. John newport langley and paul ehrlich introduced the concept of a receptor that would mediate drug action at the beginning of the 20th century. Jan 09, 2006 as we have seen, neither hill nor clark, having clearly established the physicochemical basis for analysing drugreceptor interactions, took the theory one simple stage further to explain drug antagonism in terms of competition between agonist and antagonist molecules for the same receptors, though both had thought about this possibility. Allows one to determine a rough estimate of an unlabeled ligands affinity for a receptor. A molecule, often a drug, binds to a receptor based on its steric nature. The formation of the drug receptor complex leads to a biological response. Department of physiology and pharmacology university of southern denmark denmark. As we have seen, neither hill nor clark, having clearly established the physicochemical basis for analysing drug receptor interactions, took the theory one simple stage further to explain drug antagonism in terms of competition between agonist and antagonist molecules for the same receptors, though both had thought about this possibility. The receptor s affinity for binding a drug determines the concentration of drug required to form a significant number of drug receptor complexes, and the total number of receptors may limit the maximal effect a drug may produce. A drug that inactivates a receptor is called an antagonist. Receptors determine the quantitative relationship between dose or concentration of the drug and the pharmacological e. Nonspecific conformational perturbations antagonist 3. Computer based drug designing is a fast, automatic, very low cost process. Drug receptor interactions drugs have complex shapes drugs bind to a receptor combined drug receptor interaction then allows drug to act on target tissue reversible binding occurs when drug is able to separate from cells receptor when drug is removed from receptor, effect of drug.
Data for doseresponse curves depend on the effect of the drug being examined. The receptors affinity for binding a drug determines the concentration of drug required to form a significant number of drugreceptor complexes, and the total number of receptors may limit the maximal effect a drug may produce. A drug that binds to a receptor and produces a biological response is an agonist. Textbook of receptor pharmacology second edition edited by john c. Thus, an agonist has the properties of affinity and intrinsic activity. Classification of drugs based on drug receptor interactions.
Drug concentration in the receptor compartment 40 references 41 3. Drug receptor theory also furnishes the tools for quantifying the activity of drugs in. Classical theory of antagonism the development of the classic theory of drug antagonism by gaddum, schild and arunlakshana built on the work of langley, hill and clark. One example is changes in muscle strength when different.
Reversible drug receptor complex most desirable drug can eventually be excreted requires rather weak receptor drug interactions when added together afford a stable interaction hydrogen bonds. Thus, if no receptors exist in the body for the molecules of a certain chemical substance, this substance cannot be an active and specific drug in the narrower. A receptor is a component of a cell or oganism that interacts with drugs which results in a sequence of events which lead to an observed change in function. The drug receptor interaction implies a mutual molding of drug and receptor like a lock and its matching key. Under these circumstances, null methods using equal functional responses allowed the cancellation of cellular effects for quanti. Activation of receptors is proportional to the total number of encounters of a drug with its receptor. A drug is said to be an antagonist when it binds to a receptor and prevents blocks or inhibits a natural compound or a drug to have an effect on the receptor. A drug receptor interaction occurs where a drug binds to a specific ligand for an endogenous regulatory substance. Mechanism of drug action enzyme, ion channel, transporter and receptor. These receptors may be enzymes, nucleic acids, or specialized membranebound proteins.
Read online the quantitative analysis of drug receptor interactions. A measure of tightness of chemical interaction of a drug for a receptor. The pharmacology of adrenergic receptors august 27, 2012 m. A theory of drug action based on the rate of drugreceptor combination. To design a rational drug, we must firstly find out which proteins can be the drug targets in pathogenesis. Clarkes receptor occupation theory the occupancy model was the first model put forward by clark to explain the activity of drugs at receptors quantified the relationship between drug concentration and observed effect. Drugs interact with receptors in a reversible manner to produce a change in the state of the receptor, which is then translated into a physiological effect.
Introduction to pharmacokinetics and pharmacodynamics. Clinical pharmacology and receptor theory dose response relation in psychiatric medications drug development and interactions alzheimers and parkinsons disease adverse drug effects molecular neuropharmacology receptor theory for drug effects behavioral neuropharmacology pharmacokinetic and pharmacodynamic parameters. Dissociation constant of the drug receptor complex gives an idea a bout how potent is the drug. The substance that inter acts at the receptor binding site is known as a ligand. Rigorous characterization of the receptor response system in the intact target cell is a crucial prerequisite for ultimately understanding the molecular basis for the physiological response observed in vivo, as it is only to the extent that the purified and reconstituted assembly mimics the native receptor response system that the in vitro. Mar 07, 20 emax equation from drug receptor theory duration. Consequently, the historical account of the development of receptor theory in this chapter will. Pdf today, the concept of specific receptors for drugs and transmitters lies at the very heart of pharmacology. John newport langley 18521925 and his path to a receptor theory of drug action volume 48 issue 2 andreasholger maehle. Surprisingly, it was only discovered late in the advent of science, and accepted later by the scientific community. A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Drug receptor effect drug receptor complex ligandbinding domain.
Simple occupancy theory the intensity of the response to a drug is proportional to the number of receptors occupied by that drug and that 2 a maximal response will. Drug receptor theory also furnishes the tools for quantifying the activity of drugs in a systemindependent manner, essential because drugs are almost always studied in test systems somewhat. This molecular interaction with the receptor can be modeled mathematically and obeys the law of mass action. A drug is said to be an agonist when it binds to a receptor and causes a response or effect. Frankel argued that the selective action of drugs can only be understood by assuming that certain groups in the drug molecule enter into a chemical union with the.
Department of pharmacology university college london united kingdom torben johansen, m. However, the latter process does not last too long because at some point the receptor drug complex is degraded and eliminated, and a new free receptor is synthesized. In short, a drugs geometric shape along with its electron distribution of energies must match. Download the quantitative analysis of drugreceptor interactions.
According to this view, the duration of receptor occupation determines whether a molecule is agonist, partial agonist. It is also important to understand how drugs used in the medical management of patients can alter. Occupancy theory drug and receptor interact with each other. Drug receptor definition of drug receptor by medical dictionary. List the two basic principles of the simple occupancy theory of drug receptor interaction. General rules may apply to drugs that work on receptors. Receptors are responsible for selectivity of drug action. The interaction between the drug d and receptor r is governed by the law of action.
A large category of them exerts their physiologic effects by binding with naturally selective receptor s and thus making the drug receptor interaction a widely studied subject, considering. Two state model of receptor activation theories of drug receptor interactions 10. As noted above, drug receptor interaction can generally be defined as specific, doserelated and saturable. Receptors vary greatly in structure so a specific chemical structure is required for the receptor site and a. Drug receptor interactions receptor antagonist agonist. A drug receptor is a specialized target macromolecule that binds a drug and mediates its pharmacological action. A theory of drug action is developed on the assumption that excitation by a stimulant drug is proportional to the rate of drugreceptor combination, rather than to. Most drugs combine with specific sites on macromolecules e.
Drug receptor interaction drugs interact with receptor sites localized in macromolecules which have proteinlike properties and specific three dimensional shapes. Receptor theory was propounded by alfred joseph clark, a theory of drug action based on occupation of receptors by specific drugs and the cellular function can be altered by interaction of the receptors with the drugs. A drug that binds to a receptor but does not initiate a cellular response is an antagonist. An appropriate response to the drug is chosen, and different drug doses are plotted against the response generated. The biological activity is related to the drug affinity for the receptor, i. The driving force for drug receptor interaction is the low energy state of the drug receptor complex. An illustration of the relationship between drug concentration and receptor occupancy by drug is shown in figure 1.
Drug receptor interactions an overview sciencedirect topics. Drug receptor interaction signaling molecules effectors are released by signaling cells signaling molecules that translate the drug receptor interaction into a change in cellular activity. Drug molecule binding interactions changes the receptor state and receptor function. John newport langley 18521925 and his path to a receptor theory of drug action volume 48 issue 2 andreasholger maehle skip to main content accessibility help we use cookies to distinguish you from other users and to provide you with a better experience on our websites. Receptor theory assigns mathematical rules to biological systems in order to quantify drug effects and define what biological systems can and cannot do, leading to the design of experiments that may further modify the model. Mechanism of drug action enzyme, ion channel, transporter and receptor general pharmacology. Modules 8 and 9 drug receptor theory flashcards quizlet.
Read online the quantitative analysis of drugreceptor interactions. The drug receptor theory is a fundamental theory in pharmacology. Introduction to pharmacokinetics and pharmacodynamics 3 regulation results in variation of sensitivity to drug effect from one individual to another and also determines enhancement of or tolerance to drug effects. The principles of drug design course aims to provide students with an understanding of the process of drug discovery and development from the identification of novel drug targets to the introduction of new drugs into clinical practice. As the drug concentration is increased, a progressively higher fraction of available receptors will become occupied by drug until all available receptors become bound. A minimum three point attachment of a drug to a receptor site is required. Although not all drugs act on receptors, many do and knowledge of receptor theory aids in understanding drug action and effect.
This has been extended into several conceptual frameworks eg. General theory of drugreceptor interactions springerlink. Pharmaodynamicscontd drugreceptor interactions agonist antagonist drug specificity clarks occupation theory drug. An agonist is a compound that binds to a receptor and produces the biological response. The specific binding site on a receptor may be identified and studied. Download the quantitative analysis of drug receptor interactions. Pharmacological receptor models preceded accurate knowledge of receptors by many years. Reversible drug receptor complex most desirable drug can eventually be excreted requires rather weak receptor drug interactions when added together afford a stable interaction. Gaddum described a model for the competitive binding of two ligands to the same receptor in short communication to the physiological society in 1937. Also intriguing is how this fundamental theory which has not been. In the simplest examples of drug effect, there is a relationship between the concentration of drug at the receptor. Learn vocabulary, terms, and more with flashcards, games, and other study tools.
Binding of drug to receptor is essentially the same as drug to enzyme as defined by the michelismenten equation. Drugs interact with receptors to produce a change in the state of the receptor, which is then translated into a physiological effect. These characteristics of a drug at a receptor are described by k d and ed 50 and can be obtained from ligand binding and doseresponse curves. The mechanism of drug receptor function is also described in terms of the various iterations of the ternary complex model, the twostate theory for ion channels. Sometimes, full effect is seen at a fractional receptor occupation. Two expressions for colculating receptor occupancy by antagonist in competitive drug antagonism are contrasted. Steffenhagen biological, psychogenic, and sociogenic factors in drug dependence w. Jun 19, 2017 receptor types, mechanism, receptor pharmacology, drug receptor interactions, theories of receptor pharmacology, spare receptors and new concepts like biased a slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. A constant that describes the innate ability of a drug to stimulate or activate a receptor, regardless of stimulus response coupling.
Described in this unit are procedures which can be used to define properties of drugs and receptors that transcend tissue hosts. Both ehrlich and langley had conceptualised the receptor through analogy with chemical. Theories on drug abuse selected contemporary perspectives, 30. Full text get a printable copy pdf file of the complete article 94k, or click on a page image below to browse page by page. I pharmacodynamics in pharmacology terry kenakin encyclopedia of life support systems eolss pharmacodynamics in pharmacology terry kenakin glaxosmithkline research and development, usa keywords. Molecular modeling includes computational techniques that are used to model a molecule. As a drug approaches a receptor, the receptor alters the conformation of its binding site to produce drugreceptor complex. Occupation theory drugs act on binding sites and activate them, resulting in a biological response that is proportional to the amount of drug receptor complex formed. The quantitative analysis of drugreceptor interactions. It covers the basic principles of how new drugs are discovered with.
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