Pharmacological Blog: Dose–Response Relationships
Discuss any discrepancies between your calculated EC50 values and the Ki/Kd Relationship between EC50 and. Kd. Full agonist: Kd agonist concentration is 6. Are you familiar with other types of cAMP assays? Which and what are the. Kd and spare receptors. Kd is the concentration of drug required to bind HALF of the receptors. EC50 is achieved at 5 receptors bound. Kd is MUCH greater. The relationship between dose and drug effect can be expressed relationship between receptor occupancy and response is linear, KD = EC If there . 6 between the doses producing a therapeutic effect and the doses that produce side.
Therefore, it makes sense that a drug's effectiveness, potency, is affected by how well the drug can bind to a receptor, affinity, and how it is able to cause a reaction in the receptor when bound, efficacy.
The response is equal to the effect, or Eand depends on both the drug binding and the drug-bound receptor then producing a response; thus, potency depends on both affinity and efficacy. The agonist, the ligand, drug or hormone that binds to the receptor and initiates the response is usually abbreviated A or D. Below a certain concentration of agonist [A]E is too low to measure but at higher concentrations it becomes appreciable and rises with increasing agonist concentration [A] until at sufficiently high concentrations it can no longer be increased by raising [A] and asymptotes to a maximum Emax.
The Emax is the maximum possible effect for the agonist. The term "potency" refers to the [A]50 value. Higher potency does not necessarily mean more side effects. The pharmacophore is the part of the drug molecule - the atoms and groups - that bind to the receptor; the "auxophore" are the parts of the molecule that are not directly involved in binding, but may rather interfere with binding, be essential for the arrangement of pharmacophoric elements, or may be irrelevant.
This contrasts with a quantal response, which describes an all-or-nothing response.
A graph of this relationship is known as a graded dose—response curve. Plotting the magnitude of the response against increasing doses of a drug produces a graph that has the general shape depicted in Figure A.
The curve can be described as a rec-tangular hyperbola—a very familiar curve in biology, because it can be applied to diverse biological events, such as ligand binding, enzymatic activity, and responses to pharmacologic agents.
50% of what? How exactly are IC50 and EC50 defined?
Two important properties of drugs can be determined by graded dose—response curves. The first is potency, a measure of the amount of drug necessary to produce an effect of a given magnitude. For a number of reasons, the concentration producing an effect that is fifty percent of the maximum is used to determine potency; it commonly designated as the EC Panel A is a linear graph.
Panel B is asemilogarithmic plot of the same data. Thus, therapeutic preparations of drugs will reflect the potency.Ec50 &efficacy &potency
For example, candesartan and irbesartan are angiotensin—receptor blockers that are used alone or in combination to treat hypertension. Candesartan is more potent than irbesartan because the dose range for candesartan is 4 to 32 mg, as compared to a dose range of 75 to mg for irbesartan.
An important contributing factor to the dimension of the EC50 is the affinity of the drug for the receptor. Semilogarithmic plots are often employed, because the range of doses or concentrations may span several orders of magnitude. By plotting the log of the concentration, the complete range of doses can be graphed.
50% of what? How exactly are IC50 and EC50 defined? - FAQ - GraphPad
It is also easier to visually estimate the EC The second drug property that can be determined from graded dose—response plots is the efficacy of the drug. This is the ability of a drug to illicit a physiologic response when it interacts with a receptor. Efficacy is dependent on the number of drug—receptor complexes formed and the efficiency of the coupling of receptor activation to cellular responses. Analogous to the maximal velocity for enzyme-catalyzed reactions, the maximal response Emax or efficacy is more important than drug potency.
A drug with greater efficacy is more therapeutically beneficial than one that is more potent. The quantitative relationship between drug concentration and receptor occupancy applies the law of mass action to the kinetics of the binding of drug and receptor molecules. The green symbols show measurements made with controls. The data of the experimental dose-response curve red dots extend all the way between the two control values. When fitting this curve, you need to decide how to fit the top plateau of the curve.
You have three choices: Fit the data only, ignoring the Blank control values. Average the Blank control values, and set the parameter Top to be a constant value equal to the mean of the blanks. Enter the blank values as if they were part of the dose-response curve.
Simply enter a low dose, perhaps or You can't enter zero, because zero is not defined on a log scale. The results will be very similar with any of these methods, because the data form a complete dose-response curve with a clear top plateau that is indistinguishable from the blank. I prefer the third method, as it analyzes all the data, but that is not a strong preference.
Does the EC50 equals Kd for a partial agonist? - The Student Room
Similarly, there are three ways to deal with the bottom plateau: That is the ideal situation. There is no ambiguity about what IC50 means.
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A situation where IC50 can be defined in two ways This figure shows an unusual situation where the inhibition curve plateaus well above the control values NS defined by a high concentration of a standard drug.
This leads to alternative definitions of IC Clearly, a single value cannot summarize such a curve. You'd need at least two values, one to quantify the middle of the curve the drug's potency and one to quantify how low it gets the drug's maximum effect.
The graph above shows two definitions of the IC The relative IC50 is by far the most common definition, and the adjective relative is usually omitted.