Schild plot Flashcards

(7 cards)

1
Q

competitive antagonists

A

Very important drugs e.g. pancuronium, cetirizine, propranolol

Used to inhibit the effects of a neurotransmitter or hormone

Their effects can be overcome by increasing the concentration
of the AGONIST i.e. the blockade is surmountable

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2
Q

a measure of RCA affinity?

A

The extent to which the agonist curve is shifted by the antagonist (i.e.
the amount of agonist you must add to overcome the blocking action
of the antagonist) is related to the affinity of the ANTAGONIST for the
receptor

The shift in the curves can be measured using the “dose-ratio” i.e.
the ratio of the concentration of agonist producing the same sized
response in the presence and absence of the antagonist

For a reversible competitive antagonist, the dose-ratio should
increase linearly with the concentration of the antagonist (another
way of saying you get a parallel shift in the curves)

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3
Q

how to obtain pA2?

A

Start by constructing
(log)concentration-response curves for
the agonist in the presence of several
concentrations of antagonist

This allows the pA2 to be calculated by
“Schild analysis”

It also tells us whether the antagonism is
reversible and competitive

If you don’t see a parallel.

i

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4
Q

the schild equation?

A

The Schild equation

log (dose ratio -1) = 1 x log (antagonist concentration) – log
KB

KB is the equilibrium dissociation constant (equivalent to KD) for
an antagonist measured using this technique

For a reversible competitive antagonist a plot of log (dose
ratio-1) versus log antagonist concentration (a Schild plot)
should have a gradient of 1.0 and intercept the X-axis at
(-log10KB)

For a reversible competitive antagonist:

-log10KB = pKB = pA2

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5
Q

steps to produce a schild plot?

A

Construct (log)concentration-response
curves to the agonist in the presence
of several concentrations of antagonist

From the curves read the logEC50
values for the agonist in the absence
and presence of the different
concentrations of antagonist

Calculate the EC50 values for the
agonist in the absence and presence
of the different concentrations of
antagonist

Calculate the dose ratio for each
concentration of antagonist

you should be able to complete the table:
conc of antagonist
log (antagonist)
log EC50
EC50 (M)
Dose ratio
Dose ratio-1
Log (dose ratio-1)

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6
Q

interpreting a schild plot key points:

A

A couple of important points

If the slope (gradient) of the Schild plot does not equal 1.0, (or at
least fall in the range 0.8 to 1.2) then this tells us that the antagonist
is not a reversible competitive antagonist (something else is going
on…)

Note that the pA2 obtained for the antagonist is independent of the
agonist used; it is a measure of antagonist affinity for the receptor
which is a property independent of the agonist

Often receptors are characterised by the pA2 values calculated for
different antagonists acting on them

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7
Q

kb and pa2

A

🔹 What is KB?
KB is the equilibrium dissociation constant for an antagonist — it tells you how tightly the antagonist binds to a receptor. A lower KB means the antagonist binds more tightly (higher affinity).

🔹 What is pA2? Why is it related to KB?
pA2 is a number that tells you how potent an antagonist is. It’s defined as the negative log (base 10) of the KB value:

pA2 = –log10(KB)

So if KB = 1 nanomolar (1 × 10⁻⁹ M), then pA2 = 9.

🔹 Why use pA2 instead of KB?
pA2 is just a log scale version of KB, which is easier to compare across drugs (like how we use pH instead of [H+]).

Also:

In functional experiments (using real tissues or cells), you can measure pA2 without knowing the exact binding site — which is very useful.

When the Schild plot slope is 1 (which means it’s a standard competitive antagonist), pA2 directly equals the log of KB.

🔹 Why not use KA (agonist affinity) instead?
Because:

KA (agonist affinity) depends on receptor state — agonists behave differently if the receptor is coupled to other proteins (like G-proteins).

Antagonists, on the other hand, just bind and block — they don’t activate the receptor — so KB is more stable and reliable.

That’s why KB (or pA2) is preferred when measuring true receptor affinity.

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