Pharmacological Abbreviations

Pharmacological Glossary Abbreviations (Definitions of Commonly Used Pharmacological Terms)

Agonist

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.

Allosteric Modulator

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.

Antagonist

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.

AUC

The area under the plasma (serum, or blood) concentration versus time curve.It is used in toxicology, biopharmaceutics and pharmacokinetics.

Bmax

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 preparation.

CYP

The cytochrome P450 superfamily. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The most common reaction catalyzed by cytochromes P450 is a monooxygenase reaction. RH (organic substrate) + O2 + 2H+ + 2e– → ROH + H2O. CYP families in humans divided among 18 families of cytochrome P450 genes and 43 subfamilies.

Desensitisation

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.

DMPK

(1) Drug Metabolism and Pharmacokinetics; (2) Dystrophia Myotonica Protein Kinase.

EC50

The molar concentration of an agonist that produces 50% of the maximum possible response for that agonist.

ED50

In vitro or in vivo dose of drug that produces 50% of its maximum response or effect.

Efficacy

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 (see Agonist, Partial).

ELISA

Enzyme-linked immunosorbent assay, also known as an enzyme immunoassay (EIA), is a biochemical technique used mainly in immunology to detect the presence of an antibody or an antigen in a sample.

Ex vivo

Taking place outside a living organism.

Fluorescence

A first optical system (excitation system) illuminates the sample using a specific wavelength (selected by an optical filter, or a monochromator). As a result of the illumination, the sample emits light (it fluoresces) and a second optical system (emission system) collects the emitted light, separates it from the excitation light (using a filter or monochromator system), and measures the signal using a light detector such as a photomultiplier tube (PMT). The advantages of fluorescence detection over absorbance detection are sensitivity, as well as application range, given the wide selection of fluorescent labels available today.

Fluorescence polarization

The samples in the microplate are excited using polarized light (instead of non-polarized light in FI and TRF modes). Depending on the mobility of the fluorescent molecules found in the wells, the light emitted will either be polarized or not.

Hit compound

A chemical compound that produces a result in a preliminary biochemical test indicating that the compound merits further study as part of a drug discovery project.

IC50

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%.

ID50

In vitro or in vivo dose of a drug that causes 50% of the maximum possible inhibition for that drug.

The equilibrium dissociation constant for a competitive antagonist: the molar concentration that would occupy 50% of the receptors at equilibrium.

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.

Minimum inhibitory concentration (MIC)

MIC is the lowest concentration of a chemical which prevents visible growth of a bacterium. This is in difference to the minimum bactericidal concentration (MBC) which is the concentration resulting in microbial death as defined by the inability to re-culture bacteria. The closer the MIC is to the MBC, the more bactericidal the compound.

LC-MS

Liquid chromatography-mass spectrometry. an analytical chemistry technique that combines the physical separation capabilities of liquid chromatography (or HPLC) with the mass analysis capabilities of mass spectrometry. There are a lot of mass analyzers that can be used in LC/MS. Single Quadrupole, Triple Quadrupole, Ion Trap, TOF (time of Flight) and Quadrupole-time of flight (Q-TOF).

Lead compound

(1) a compound that has been selected from a group of hit compounds based on qualities such as the intensity of the biochemical effect that occurs when the compound is present (efficacy), or the absence of coincidental effects (specificity);
(2) a chemical compound that has pharmacological or biological activity and whose chemical structure is used as a starting point for chemical modifications in order to improve potency, selectivity, or pharmacokinetic parameters.

Luminescence

The difference with fluorescence is that the light emitted by the samples is the result of a chemical or biochemical reaction (instead of being the result of excitation by light). Luminescence plate readers are simpler optically than fluorescence readers, as they don't require a light source, just a light detector. Typically, the optical system consists in a light-tight reading chamber, and PMT detector measuring the light emitted by the samples during the reaction. Common applications include luciferase-based gene expression assays, as well as cell viability and cytotoxicity assays based on the luminescent detection of ATP.

Nude mouse

A laboratory mouse from a strain with a genetic mutation that causes a deteriorated or absent thymus, resulting in an inhibited immune system due to a greatly reduced number of T cells. The genetic basis of the nude mouse mutation is a disruption of the FOXN1 gene. Most strains of nude mice are slightly "leaky" and do have a few T cells, especially as they age.

Non-Specific Binding

The proportion of radioligand that is not displaced by other competitive ligands specific for the receptor. It can be binding to other receptors or proteins, partitioning into lipids or other things.

Specific Binding

The proportion of radioligand that can be displaced by competitive ligands specific for the receptor.t½ The biological half-life of a drug or radioligand in vitro or in vivo. In vitro, the t½ of the effect of a drug is the time taken for the response to a drug to decline to half the original response. In radioligand binding, the t½ can be used to measure the dissociation rate of a radioligand from its receptor, therefore it is the time taken for the amount of radioligand bound to the receptors to decline to half its original level. In vivo, t½ refers to the metabolic half-life of a drug or radioligand, i.e. the time taken for the concentration of a drug in plasma to decline to half its original level.