The central dogma of receptor pharmacology is that a drug effect is directly proportional to the number of receptors that are occupied. There have been several major theories that have been proposed to provide a theoretical basis for understanding, modeling, and thereby predicting, drug response. The bond formed is so very strong that detachment of the ligand is very hard and nonspontaneous. This type of bonding is the strongest form of bond that can be formed between a ligand and a receptor. For the love of physics walter lewin may 16, 2011 duration. Thus, the operational model has supplanted anal ysis of drugreceptor interaction in functional systems whereas the extended ternary complex model is used. Dissociation constant of the drugreceptor complex gives an idea a bout how potent is the drug. Receptors vary greatly in structure so a specific chemical structure is required for the receptor site and a. Receptor theory is the application of receptor models to explain drug behavior. Receptor interaction alters the receptor proteins threedimensional structure, triggering signal transduction processes within the cell and resulting in a biological effect nonreceptor interaction directly target enzymes, carrier proteins like ion transporters, ion channels, dna, and cellular structures like microtubules. The classical interaction theory dictates that receptors occupation is directly.
A neurotransmitter has a specific shape to fit into a receptor site and cause a pharmacological response such as a nerve impulse being sent. The covalent interaction explains the drugs long duration of action. A drugs ability to affect a given receptor is related to the drugs affinity probability of the drug occupying a receptor at any given instant and intrinsic efficacy intrinsic activitydegree to which a ligand activates receptors and leads to cellular response. Three of the most widely known of these schemes are described as follows. After attachment to a receptor site, a drug may either initiate a response or prevent a response from occurring. When the drug leaves, the receptor returns to the nonactivated inactive or resting state and this is essential for further response cycles. It will be seen that the theory of binding and the methods used to quantify. The mechanism of drug receptor function is also described in terms of the various iterations of the ternary complex model, the two. The drugs atomic configuration must allow it to bind with the target, analogous to a. Theories on drug abuse selected contemporary perspectives editors.
The interaction of the ligand at its binding site on the. The pharmacologic effect of the drug depends on the percentage of the receptors occupied. Pdf drugs by definition, are characterized as those agents that can bring a. It does not alter the activity of the receptor and does not give the receptor a new function. Theories of drug receptor interaction receptor antagonist. A drug that binds to a receptor but does not initiate a cellular response is an antagonist.
Classical receptor theory combines two independent parts to describe drug action. General theory of drugreceptor interactions springerlink. Molecular modeling includes computational techniques that are used to model a molecule. With the possible exception of the general anesthetics, such drugs must possess a high structural specificity to. 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. A minimum three point attachment of a drug to a receptor site is required. A theory need not be correct or even visibly sensible. Thus, an agonist has the properties of affinity and intrinsic activity. The basic form of black and leffs 18 operational model of agonism is based on the observation. Ppt receptor theory powerpoint presentation free to. A drugs affinity and activity are determined by its chemical structure. The neurotransmitter is similar to a substrate in an enzyme interaction. Following clarkes and ariens drug receptor theories. The biological activity is related to the drug affinity for the receptor, i.
Microemulsions potential carrier for improved drug delivery jha s. 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. Pharmacological receptor models preceded accurate knowledge of receptors by many years. As noted above, drug receptor interaction can generally be defined as specific, doserelated and saturable. The number of drugreceptor interaction per unit time determines the intensity of the response. Drugreceptor interactions involve all known types of bond. Metabophores drugreceptor theories lock and key hypothesis. The driving force for drugreceptor interaction is the low energy state of the drugreceptor complex. Receptor theory and its role in drug therapy article. Drug it is a natural or synthetic substances which has a physiological effects when administered into the body. As the drug concentration is increased, a progressively higher fraction of available receptors will become occupied by drug until all available receptors become bound. 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. Activation of receptors is proportional to the total. 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.
Initially, the absence of drug in the receptor binding pocket drives the binding reaction toward formation of drugreceptor complexes. 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. Pharmacodynamics in pharmacology encyclopedia of life. The formation of the drugreceptor complex leads to. 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. Occupancy theory rests on the concept that the proportion of occupied receptors is related to the effect of the. A drug that binds to a receptor and produces a biological response is an agonist.
Drug molecule binding interactions changes the receptor state and receptor function. Drugtarget interaction this implies a coming together of the drug with its target or more specifically a small part of the target. Receptor theory of drug action deranged physiology. When the ligand approaches the receptor in an appropriate distance, a bond is formed, and then the drug action happens. Although not all drugs act on receptors, many do and knowledge of receptor theory aids in understanding drug action and effect. A drug that inactivates a receptor is called an antagonist.
A drug that activates a receptor is called an agonist. Microemulsions potential carrier for improved drug delivery. For full agonists, the doseresponse curves for receptor binding and each of the biological responses should be comparable. A drug receptor is a specialized target macromolecule that binds a drug and mediates its pharmacological action. Agonist, antagonist and theories of drug receptor interaction presented by abhishek ghara 1st year m. A theory of drug action based on the rate of drugreceptor. When a drug binds to a receptor, it mimics or blocks the actions of the usual endogenous regulatory molecules, either increasing or decreasing the rate of the physiologic activity normally controlled by that receptor. Substrate or drug binding to the receptor induces 3 dimensional conformational. Learn vocabulary, terms, and more with flashcards, games, and other study tools. There have been several major theories that have been proposed to provide a theoretical basis for understanding. Theories of aging chapter 2 theories of aging chapter 2 outline mechanisms of aging general theories of aging a. Alfred joseph clark was the first to quantify druginduced.
Rate theory the response is proportional to the rate of drugreceptor complex formation. Drugs act on the cell membrane by physical andor chemical. Computer based drug designing is a fast, automatic, very low cost process. Drug receptor interaction drugs interact with receptor sites localized in macromolecules which have proteinlike properties and specific three dimensional shapes. Drug receptor interactions an overview sciencedirect. Pdf in presentday pharmacology and medicine, it is usually taken for granted. The drugreceptor interaction can be described as follows. An illustration of the relationship between drug concentration and receptor occupancy by drug is shown in figure 1. General rules may apply to drugs that work on receptors. Patons rate theory this model describes the effect is produced by the drug molecules based on the rates of association and dissociation of drugs to and from the receptors. Drug receptor interactions an overview sciencedirect topics. The receptor concept, which is about a century old and undeniably represents pharmacologys big idea rang, 2006, forms the basis of our current mechanism of drug action theories maehle et al. 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 the proportion of receptors occupied by the drug.
The drug molecule must fit into the receptor like a key fits into the lock drugreceptor theories hypothesis of clark. 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. 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. Drugreceptor interactions clinical pharmacology msd. Theories of drug receptor interactionsby lee eun jin 2. These receptors may be enzymes, nucleic acids, or specialized membranebound proteins. Drugreceptor interactions drugs can have two fates at the receptor site. Mollie sayers helen wallenstein pearson nida research monograph 30 march 1980 department of health and human services public health service alcohol, drug abuse, and mental health administration national institute on drug abuse division of research 5600. Drugligand receptor interaction langley 1878 drug drugreceptor complex ligandbinding domain k1 effector.
All of these actions are attributable to interaction of the drug with the receptor. This molecular interaction with the receptor can be modeled mathematically and obeys the law of mass action. The interaction of a drug molecule with its receptor can be represented in the manner shown in figure 22, where. Steric factors determined by the stereochemistry of the receptor site surface and that of the drug molecules are, therefore, of primary importance in determining the nature and the efficiency of the drugreceptor interaction. Thus, the operational model has supplanted analysis of drugreceptor interaction in functional systems whereas the extended ternary complex model is used. John newport langley and paul ehrlich introduced the concept of a receptor that would mediate drug action at the beginning of the 20th century. When a drug is added to 2 a compartment containing the receptor, then the concentration gradient controls the movement of drug molecules. Drugs with short duration of action generally have weaker bonds. Drug designing by using these modeling techniques is referred to as computeraided drug design. This unit provides a historical perspective of classical receptor theory and the currently used operational model of drug effects. Theories of drug receptor interaction free download as powerpoint presentation. Common to all receptor theories, is the postulate that an agonistic drug combines with a site on a receptor and the receptor becomes activated, so triggering a response from the cell. Classification of drugs based on drugreceptor interactions.
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