Drugreceptor interactions involve all known types of bond. The analogy between enzymatic kinetics and drug receptor interaction lent to receptor theory an analytical feature, most of theoretical. As a drug approaches a receptor, the receptor alters the conformation of its binding site to produce drugreceptor complex. John newport langley and paul ehrlich introduced the concept of a receptor that would mediate drug action at the beginning of the 20th century. Drug it is a natural or synthetic substances which has a physiological effects when administered into the body. Receptors vary greatly in structure so a specific chemical structure is required for the receptor site and a. Combining equations 23 and 24 gives the following equation for tissue.
Mechanism of drug action drug receptor interactions howmed. John newport langley and paul ehrlich introduced the concept of a receptor that would mediate drug action at. Another theory involves the partial agonist being able to bind to the receptor in more than one place, so one method of binding would produce an agonist effect and the other an antagonist effect. Computeraided drug design cadd is an exciting and diverse discipline where various aspects of applied and basic research merge and stimulate each other. Sometimes this area is referred to as receptor theory but this term covers much that is closer to empirical description than to physics, and therefore is not relevant.
Drug receptor theory, quantification of drug effect definition mathematical models of the interaction between drugs and receptors, based on michaelismenten enzyme kinetics, are utilized to create the quantitative tools currently used in receptor pharmacology to quantify drug effect in biological systems. Pdf today, the concept of specific receptors for drugs and transmitters lies at the very heart of pharmacology. Agonist, antagonist and theories of drug receptor interaction presented by abhishek ghara 1st year m. This chapter provides a synopsis of the development of the receptor concept to explain differential tissue distribution and ultimate specificity of drug action. Together with structures of the prototypical gpcr rhodopsin, solved structures of other liganded gpcrs promise to provide insights into the structural basis of the superfamilys biochemical. 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. In this article, i shall describe the evolution of attempts to describe the physics of receptors in terms of equations. Drug receptor definition of drug receptor by medical dictionary. Feb 25, 2018 theories of drug receptor interaction 1. Steffenhagen biological, psychogenic, and sociogenic factors in drug dependence w. The mathematical model that describes drug concentration and receptor binding can be applied to dose drug concentration and response or effect, providing the following assumptions are met.
Erlich introduced the term receptor around 1900, he was considering the mechanism of. However, combining that parameter with atomic excess charge on aliphatic. Drug receptor interaction drugs interact with receptor sites localized in macromolecules which have proteinlike properties and specific three dimensional shapes. As the drug concentration is increased, a progressively higher fraction of available receptors will become occupied by drug until all available receptors become bound. Uncompetitive antagonists, when the antagonist binds to the receptor irreversibly and is not released until the receptor is saturated.
The classical interaction theory dictates that receptors occupation is directly. Introduction a drug receptor is any biological component capable of binding a drug molecule and generating a cellular effect. This balance between the two would result in only a proportion of the receptors being activated, hence, the partial antagonistic effect katzung, 2001. The pharmacological effect produced by activation of a receptor by the drug.
The assumption made in classical receptor theory is that a drug. Receptor theory of drug action deranged physiology. 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. These concepts are important in the study of basic pharmacologic data regarding different compounds with affinity for the same receptor. Dec 01, 2011 crucial as molecular sensors for many vital physiological processes, seventransmembrane domain g proteincoupled receptors gpcrs comprise the largest family of proteins targeted by drug discovery. It will be seen that the theory of binding and the methods used to quantify drug effect are. In the study of the interaction between pharmacologically active molecules and different types of receptoreffector systems often designated as molecular pharmacology an important role is played by theoretical mathematical models with which these interactions can be described clark, 1926, 1937. The amount of antagonist or main drug that binds with the receptor will depend on the concentrations of each one in the plasma. For a given drug, the magnitude of response is directly proportional to the fraction of total receptor sites occupied by drug molecules i.
C the drug concentration required to occupy 50% of receptors d drug concentration that results in halfmaximal physiological response. Here, a general twostate receptor model and corresponding quantitative forms are proposed that unify three. An illustration of the relationship between drug concentration and receptor occupancy by drug is shown in figure 1. Joseph clark, who similarly helped to establish the receptor theory of drug action. The concentration of the drug that will produce 50% of the maximum pharmacological effect ed50, we will discuss this term later. A drug is said to be an agonist when it binds to a receptor and causes a response or effect.
Classification of drugs based on drugreceptor interactions. 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. Affinity values 1k d for the individual receptor subtypes and drug concentration a lead to the fractional receptor occupation by application of mass action. The interaction of a drug molecule with its receptor can be represented in the manner shown in figure 22, where. These concepts are important in the study of basic pharmacologic data regarding different compounds with. Thus, the three curves of concentrationeffect data are obtained. The drug receptor interaction implies a mutual molding of drug and receptor like a lock and its matching key. Nonspecific conformational perturbations antagonist 3. Drug molecule binding interactions changes the receptor state and receptor function.
Occupancy theory rests on the concept that the proportion of occupied receptors is related to the effect of the drug eg. 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. 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. Equation 1 therefore relates the concentration of drug and the proportion of. Known as the lipoid theory of cellular depression, it was based on the observation.
A relationship between available drug concentration and the proportion of receptors occupied was quickly advanced which implied that drugreceptor interactions obey mass action principles, in a manner analogous to enzymesubstrate interactions. 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. An illustration of the relationship between drug concentration and receptor occupancy by drug is shown in. The interaction of the ligand at its binding site on the. Mar 07, 20 emax equation from drug receptor theory duration. The number of drug molecules is assumed to be much greater than the number of receptor sites.
Drug receptor interactions an overview sciencedirect topics. Drug designing by using these modeling techniques is referred to as computeraided drug design. Drug receptor subtypes and ingestive behaviour is designed to guide students and investigators through a number of different neurotransmitter systems and provide them with the latest information on the identities of receptor subtypes most relevant in the study of ingestive behaviour. Diffusion and drug concentration in receptor compartments 145 7. A drug that binds to a receptor but does not initiate a cellular response is an antagonist. 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. In figure 11, a and b, drug a has a higher affinity for the receptor than drug b. 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. Theories on drug abuse selected contemporary perspectives, 30.
Ppt receptor theory powerpoint presentation free to view. Isolated muscle fibers pilocarpine contraction and atropine inhibition. Balis, in principles of clinical pharmacology second edition, 2007. However, it does block the site preventing any other agonist or the normal. Thus, an agonist has the properties of affinity and intrinsic activity. Drug receptor theory also furnishes the tools for quantifying the.
The identification of receptor molecules by structural, functional, and ligand binding criteria will also be discussed. K d also represents the concentration of drug needed to bind 50% of the total receptor population. The effect continues until the drug is excreted or new receptor is generated. D d drug r receptor, dr drug receptor complex k 1 rate for association and k 2 rate for dissociation. The receptor theory is as important and basic to pharmacology as the atomic theory is to physical sciences. As such, it will prove enormously useful to all engaged in.
As noted above, drug receptor interaction can generally be defined as specific, doserelated and saturable. The quantification and differentiation of the drug receptor theory, c. Drug receptor interactions an overview sciencedirect. In the early stage of a drug discovery process, researchers may be faced with little or no structure activity relationship sar information. Competitive antagonists, if they compete with the main drug to bind with the receptor. The drugreceptor concept of drug action and the receptor occupation theory describe a graded doseeffect relationship, in which the responding system is capable of showing a progressively increasing effect with increasing dose or drug concentration. In irreversible binding, very strong covalent bonds are present, which prolongs the effects of drug. Prolong contact of tissues with the agonists results in decreased number of receptors in the tissues called down regulation of receptors. Pdf drugs by definition, are characterized as those agents that can. Drug receptor binding an overview sciencedirect topics. Rigorous characterization of the receptorresponse 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 receptorresponse system that the in vitro. 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. However, for ligand binding models justification is provided by theory of receptor occupancy.
Pharmacological receptor models preceded accurate knowledge of receptors by many years. This molecular interaction with the receptor can be modeled mathematically and obeys the law of mass action. The quantitative analysis of drugreceptor interactions. Gaddum described a model for the competitive binding of two ligands to the same receptor in short communication to the physiological society in 1937. When a drug d combines with a receptor r, it does so at a rate which is dependent on the concentration of the drug and the concentration of the receptor. An overview of pharmacodynamic modelling, ligandbinding. The drug receptor concept of drug action and the receptor occupation theory describe a graded doseeffect relationship in which the responding system is capable of showing progressively increasing effect with increasing dose or drug concentration. Jan 27, 2017 the mathematical model that describes drug concentration and receptor binding can be applied to dose drug concentration and response or effect, providing the following assumptions are met.
Receptor theory in pharmacology terry kenakin assay development compound profiling, glaxosmithkline research and development, 5 moore drive, research triangle park, nc 27709, usa pharmacological receptor theory is discussed with clark is credited with being the originator. First postulated by john langley 1878 established after his experiments using nicotine and curare analogues on muscle contraction. Learn vocabulary, terms, and more with flashcards, games, and other study tools. Drug receptor subtypes and ingestive behaviour 1st edition. The chemical forces of attraction that cause the drug to associate with the receptor. The drug receptor interaction is usually reversible.
The drugreceptor interaction implies a mutual molding of drug and receptor like a lock and its matching key. Aug 31, 2018 receptors are the macromolecule or binding site located on the surface or inside the effector cell that serve to recognize the signal molecule or drug and initiate the response to it, but they don. In quantitative pharmacology, multiparameter receptor models are needed to account for the complex nonlinear relationship between fractional occupancy and response that can occur due to the intermixing of the effects of partial receptor activation and postreceptor signal amplification. Receptor theory is the application of receptor models to explain drug behavior. D d drug r receptor, dr drugreceptor complex k 1 rate for association and k 2 rate for dissociation. The four different types of receptor part 1 duration. An antagonist drug interacts with the receptor site and blocks or depresses the normal response for that receptor because it only partially fits the receptor site and can not produce an effect.
As the concentration of a drug increases, the drug will combine with receptors for which it has lower affinity. A drug receptor interaction occurs where a drug binds to a specific ligand for an endogenous regulatory substance. Receptor theory was propounded b y alfred joseph clark, a theory of drug ac on based on occupa on of receptors by speci c drugs and the cellular func on can be altered by. Molecular modeling includes computational techniques that are used to model a molecule. Statistical assessment of biological significance from data 198 8. Macromolecular nature of drug receptors the bestcharacterized drug receptors are cont.
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