A drug that binds to and activates a receptor. Can be full, partial or inverse. A full agonist has high efficacy, producing a full response while occupying a relatively low proportion of receptors. A partial agonist has lower efficacy than a full agonist. It produces sub-maximal activation even when occupying the total receptor population, therefore cannot produce the maximal response, irrespective of the concentration applied. An inverse agonist produces an effect opposite to that of an agonist, yet binds to the same receptor binding-site as an agonist.
A drug that binds to a receptor at a site distinct from the active site. Induces a conformational change in the receptor, which alters the affinity of the receptor for the endogenous ligand. Positive allosteric modulators increase the affinity, whilst negative allosteric modulators decrease the affinity.
A drug that attenuates the effect of an agonist. Can be competitive or non-competitive, each of which can be reversible or irreversible. A competitive antagonist binds to the same site as the agonist but does not activate it, thus blocks the agonist’s action. A non-competitive antagonist binds to an allosteric (non-agonist) site on the receptor to prevent activation of the receptor. A reversible antagonist binds non-covalently to the receptor, therefore can be “washed out”. An irreversible antagonist binds covalently to the receptor and cannot be displaced by either competing ligands or washing.
Receptor autoradiography may be used to determine the tissue localization of a radioactive substance, either introduced into a metabolic pathway, bound to a receptor or enzyme, or hybridized to a nucleic acid. The use of radiolabeled ligands to determine the tissue distributions or localization of receptors in either in vivo, ex vitro or in vitro experiments.
The maximum amount of drug or radioligand, usually expressed as picomoles (pM) per mg protein, which can bind specifically to the receptors in a membrane preparation. Can be used to measure the density of the receptor site in a particular membrane preparation or tissue section.
Used to determine the Ki value from an IC50 value measured in a competition radioligand binding assays.
A reduction in response to an agonist while it is continuously present at the receptor, or progressive decrease in response upon repeated exposure to an agonist.
The molar concentration of an agonist that produces 50% of the maximum possible response for that agonist.
in vitro, ex vitro or in vivo dose of drug that produces 50% of its maximum response or effect.
Describes the way that agonists vary in the response they produce when they occupy the same number of receptors. High efficacy agonists produce their maximal response while occupying a relatively low proportion of the total receptor population. Lower efficacy agonists do not activate receptors to the same degree and may not be able to produce the maximal response.
Taking place outside a living organism.
Drug of interest is injected into a living organism but binding assay using radiolabeled probe is done in vitro .
Half-life (t½) is an important pharmacokinetic measurement. The metabolic half-life of a drug in vivo is the time taken for its concentration in plasma to decline to half its original level. Half-life refers to the duration of action of a drug and depends upon how quickly the drug is eliminated from the plasma. The clearance and distribution of a drug from the plasma are therefore important parameters for the determination of its half-life.
Intra-arterial route of drug administration.
In a functional assay, the molar concentration of an agonist or antagonist which produces 50% of its maximum possible inhibition. In a radioligand binding assay, the molar concentration of competing ligand which reduces the specific binding of a radioligand by 50%.
Intracerebral route of drug administration.
Intracerebroventricular route of drug administration.
in vitro or in vivo dose of a drug that causes 50% of the maximum possible inhibition for that drug.
Intradermal route of drug administration.
Intragastric route of administration.
Intramuscular route of drug administration.
Taking place in a coplin jar, test-tube, culture dish, 96-well plate, tissue section or elsewhere outside a living organism.
Taking place within a living organism.
Intraperitoneal route of drug administration.
Intrathecal route of drug administration.
Intravenous route of drug administration.
The dissociation constant for a radiolabeled drug determined by saturation analysis. It is the molar concentration of radioligand which, at equilibrium, occupies 50% of the receptors.
The inhibition constant for a ligand, which denotes the affinity of the ligand for a receptor. Measured using a radioligand competition binding assay, it is the molar concentration of the competing ligand that would occupy 50% of the receptors if no radioligand was present. It is calculated from the IC50 value using the Cheng-Prusoff equation.
See Allosteric Modulator.
See Silent Antagonist.
The proportion of radioligand that is not displaced by other competitive ligands specific for the receptor. It can be binding to other receptors.
Measure of the potency of an antagonist. It is the negative logarithm of the molar concentration of an antagonist that would produce a 2-fold shift in the concentration response curve for an agonist.
The negative logarithm of the EC50 or IC50 value.
The negative logarithm of the EC50 value
The negative logarithm of the IC50 value.
The negative logarithm of the KB value.
The negative logarithm of the Kd value.
The negative logarithm of the Ki value.
Oral (by mouth) route of drug administration.
See Allosteric Modulator.
A measure of the concentrations of a drug at which it is effective.
Subcutaneous route of drug administration.
The proportion of radioligand that can be displaced by competitive ligands specific for the receptor. Non-specific binding is subtracted from Total Binding to yield Specific Binding.
A drug that attenuates the effects of agonists or inverse agonists, producing a functional reduction in signal transduction. Affects only ligand-dependent receptor activation and displays no intrinsic activity itself. Also known as a neutral antagonist.
In the periphery of the body (not in the central nervous system – see Useful Abbreviations).
Biological half-life (see Half-life).
The proportion of radioligand that is bound to a specific receptor without the presence of competitive ligands.