PA2 VALUE

DRUG ANTAGONISM
• ANTAGONIST have positive affinity for a particular receptor but
negative intrinsic activity
• TYPES OF ANTAGONISM
 Chemical type
Physiological type
Receptor
i) Competitive nature
ii) Non Competitive nature
PHARMACOLOGICAL SCALES TO
EXPRESS
DRUG ANTAGONISM
COMPETITIVE NON
ANTAGONISM COMPETITIVE
ANTAGONISM

PA2 VALUE PD’2 VALUE

COMPETITIVE ANTAGONISM
• Characterized by
1. Rightward parallel shift of DRC
2. Surmountable maximum response
3. No change in slope of curve
• Rightward parallel shift signifies that
greater concentration of agonist is
required to produce same EC50 which
was produced without the presence of
antagonist
 PAX SCALE
• It is a pharmacological scale used to express drug antagonism.
• Proposed by H.O Schlid (1974)

PAx is defined as negative logarithm of molar concentration of

antagonist, in presence of which X multiple dose of agonist is required
to produce same effect as produced in absence of antagonist.
 PA2 is defined as negative logarithm of molar concentration of
antagonist, in presence of which 2 multiple dose of agonist is required
to produce same effect as produced in absence of antagonist.

PA10 is defined as negative logarithm of molar concentration of

antagonist, in presence of which 10 multiple dose of agonist is
required to produce same effect as produced in absence of antagonist.
EXAMPLE
For guinea pig uterus contraction
Agonist is histamine whose actions can be
antagonized by mepyramine.
PA2 value of mepyramine is 10.02
50% response by histamine alone can be
produced at 3µg/ml
Now, according to pa2 value of
mepyramine if 10-10 M is added than to
produce same 50% response histamine
concentration has to be doubled i.e we
have to use 6µg/ml of histamine

Here, antagonism if of competitive nature

METHOD TO FIND OUT PA2 VALUE
1) Find out dose ratio from the given formula

2) Find out log(dose ratio-1)

3) Plot graph of –ve log of molar concentration of antagonist on x axis
and log(dose ratio-1) on y-axis
4) Intercept of straight line obtained on x-axis gives Pa2 value
5) Pa10 value can also be shown from graph
Intercept
APPLICATIONS OF PA2 value
The activity and relative specificity of antagonists
can be found out by comparing two PA2 values
Two vertical lines represent pA2 scales for
antagonists of histamine and acetylcholine. The
activity of an antagonist towards these drugs is
indicated by its position on the scale. Points on the
two scales referring to the same antagonist are
joined.
HORIZONTAL LINE indicates LACK OF SELECTIVITY
Eg pethidine
STEEP LINE indicates SELECTIVITY and SLOPE the
magnitude
Eg Neo-Antergan (40,000 times as active against
histamine as it is against acetylcholine .)
• Type of antagonism can be found out by (pA2 – pA10), if the
difference is 0.95 than the antagonism is of competitive nature.

• PA2 is always same for the particular antagonist at a particular

receptor.
if PA2 values are different in different tissue than it is suggestive that
different receptors are involved
Eg PA2 of Ach atropine in rat abdominus is 4.0 diff. receptor involved
PA2 of Ach atropine in g.pig ileum is 8.1
PA2 of Ach atropine in frog auricle is 8.3 same receptor involved
 The pA2 value for a particular antagonist is always same for same
tissue preparation used irrespective of type of agonist used
mepyramine
as antagonist
Histamine
2(2pyridyl)ethylamine
As agonist
As agonist

Pa2 = 10.02 Pa2 =10.02

EXPERIMENT
AIM To determine pa2 value of prazosin using rat anococcygeus
muscle (by schild’s plot method)

APPARATUS: Organ bath, rat anococcygeus muscle strip, frontal writing

lever, recording drum
PSS: Tyrode solution
Basal tension on tissue: 1 gm
Magnification of response: 10 times
Drugs used:
1) Phenylephrine (PHE)
2) Prazosin

PHE is a1 adrenoceptor agonist and stimulates the contraction of rat

anococcygens muscle strip
Prazosin is a1 adrenoceptor antagonist and stimulates relaxation of rat
anococcygens muscle strip

The type of antagonism between the above two is of competitive

nature
PROCEDURE
1) The anococcygeus muscle was removed from male albino rats
weighing 250-350 g killed by a sharp blow to the head and
exsanguination.
2) Tissue is mounted in organ tube and dipped in Tyrode solution
3) Tissue is allowed to stabilize for 30 minutes and repeated wash is
given with PSS every 10 minutes
4) DRC of PHE alone is taken till maximum response is obtained
5) Now varying concentration of prazosin is added with PHE and
respective DRC are taken till maximum response is obtained.
6) Dose ratio is obtained and log(X-1) is found out
7) Schlid plot is plotted on graph
8) Intercept is found out and PA2 value is found out
OBSERVATIONS
The DRC curve of PHE in absence and in
presence of varying concentration of antagonist
Prazosin is constructed
Following are its features :
1. Rightward parallel shift of DRC
2. Surmountable maximum response
3. No change in slope of curve

THIS INDICATES COMPETITIVE ANTAGONISM

By calculating dose ratio(X) and log(X-1)
Schild plot is constructed and pa2
Value is found out from the intercept on
x axis

From intercept the pa2 value of prazosin

Was found out to be 0.85±0.07
RESULTS
1) It is proved that the antagonism nature between PHE and prazosin
is competitive.

2) PA2 value of prazosin on rat anococcygeus muscle was found out to

be 0.85±0.07
CONCLUSION
• Both prazosin and PHE are selective for the a1 adrenoreceptor.
• Since PHE acts selectively on a1 adrenoreceptor, prazosin
competitively blocked its effects
• Straight line is obtained by schild plot
• Intercept of schlild on x axis can readily provide PA2 value
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