The meaning of pA2 is the affinity of the antagonist to the receptor (4) . In the same way, the value of pA1/2 is a negative logarithm of the concentration of a potentiator, which requires a halving of the concentration of agonist so as to induce a given response.
What is pA2 used for?
The Schild analysis is undoubtedly the most frequently used powerful diagnostic tool to investigate the nature of an antagonist and, consequently, to evaluate its potency, often expressed as pA2.
What is the pA2 of a drug?
In the field of biochemistry, a pA2 value determines the important relationship between two drugs “competing” for effect on the same receptor. ... The pA2 value indicates the concentration of antagonist when double the agonist is required to have the same effect on the receptor as when no antagonist is present.
What does a high pA2 value mean?
The higher the value for pA2, the higher the affinity of B is to its receptor . For graphic. analysis, one can plot log (DR–1) against log ([B]), yielding a linear relationship that.
How do you calculate kd from pA2?
Measure- ments of dose-ratio are commonly used to calculate an an- tagonist equilibrium constant and Schild devised the term pAX to describe log(1/[B]) for a dose-ratio of X, so pA2=7log (KD) .
What does pD2 value indicate?
pD2′ value • Measures the affinity of either non competitive or irreversible competitive antagonist for a specific receptor • Defined as –log(B) which will decrease the maximum effect of agonist by 50% • Higher the pD2 value ,higher the potency.
What is IC value?
The half maximal inhibitory concentration (IC 50 ) is a measure of the potency of a substance in inhibiting a specific biological or biochemical function. ... The biological component could be an enzyme, cell, cell receptor or microorganism. IC 50 values are typically expressed as molar concentration.
How is pD2 calculated?
pD2 value ( pD2 = -log EC50 ) was calculated using indometazine in guinea pig trachea. This bioassay record (AID 80765) reports results from the above primary citation.
What is pA in pharmacology?
The key principle is that the same sub-maximal response to an agonist is measured first in the absence of antagonist and then in its presence, using a greater concentration of agonist. ...
What does a Schild plot tell you?
Specifically, a method (Schild analysis) first described almost 60 years ago allows us to determine the equilibrium constant for binding of a competitive antagonist acting at a particular receptor (Schild, 1949; Arunlakshana and Schild, 1959).
How do you tell if a drug is an agonist or antagonist?
An agonist is a drug that binds to the receptor, producing a similar response to the intended chemical and receptor . Whereas an antagonist is a drug that binds to the receptor either on the primary site, or on another site, which all together stops the receptor from producing a response.
How do you interpret EC50?
EC 50 is a measure of concentration, expressed in molar units (M), where 1 M is equivalent to 1 mol/L. The EC 50 of a graded dose response curve therefore represents the concentration of a compound where 50% of its maximal effect is observed.
What does a negative pA2 mean?
pA 2 is a 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 .
How do you calculate kd from IC50?
KD = the affinity constant, defined as the equilibrium concentra- tion of labeled ligand that occupies 50% of receptor sites in the absence of competition. By simple rearrangement we can express the Cheng-Prusoff equation in the form: IC50 = (([Ki]/KD) × [L]) + Ki (i.e., in the format y = mx + c) .
Can IC50 be lower than KD?
The first-order rate constant for the conversion of the encounter complex to the covalent complex is called k inact , and the second-order rate constant for the overall reaction is k inact /K i . In cases like this, it may be possible for IC 50 to be lower than K i . Given sufficient time, IC 50 can reach the limit of (1/2)[E].
How do you calculate KD in pharmacology?
To determine KD, a fixed mass of membranes (with receptor) are incubated with increasing concentrations of a radioligand until saturation occurs . At saturation, Bmax is determined (maximum receptor number) and half of this is used to determine KD (Fig.
