Is Asarone a Tranquillier - Indian Journal of Physiology and

January 1968
d. J. Physiot, & PharmacoJ.
Y. L S. . These
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IS ASARONE A TRANQUILLISER?
Sir,
du
yal,
iacology,
lege, New Delhi.
adrenocortical steroids.
k in the mouse. Allergie
stress factors of asthma
24:302, 1953.
. immunity
and
hyper-
luble glllcocorticoids.
o rat. J.Physiol. 142:
ma. lilt.
Arch. Allergy.
I have read with some interest Banerjee's letter published in the October, 1967 issue of
your Journal (1). He has raised several points and has misquoted me and my co workers from
our report (9). According to Banerjee, Dandiya and coworkers (9) stated in 1959 that "asarone
is not responsible for enhancing the barbiturate induced hypnosis exhibited by Acorus oil".
In fact what was actually written there reads. "It seems unlikely that asarone is responsible for
the activity of Acorus oil since it is present to the extent of approximately
80% in the Indian oil
and about 7% in the European oil".
While in the actual communication,
only an opinion is
expressed about the unlikelyhood of activity residing in asarone, Bannerjee has attributed
a
categorical statement to these authors, which was never made.
Moreover, this opinion was
expressed by these workers (9) before any pharmacological
testing of asarone was made and
this was based on the reports regarding difference in the asarone content of tne Acorus oil from
Europeon and Indian varieties of Acorus Calamus.
Banerjee has found it difficult to understand the report of Sharma er al (16), "~asaronc ap pears to be more potent than asarone" and what was reported by Dandiya and Menon (5)
that "asarone was more potent than ~-asarone".
If Banerjee had cared to read these statements in the context each had been made in the respective papers, it should not have been difficult for him to understand. Potency of a substance as described in relationship
to the response
one is looking for.
In the earlier communication
(16), a comparative
study was made
between the action of asarone and ~·--asarone as regards their hypnotic potentiating
property,
hypothermic action, anticonvulsant properties as seen against electroshock, picrotoxin or Metrazol induced convulsions
and influence on conditioned avoidance response, while in the latter
communication
(5) these two drugs were compared for their influence on the action of resperine
and chlorpromazine
in conditioned avoidance response, fighting behaviour of mice and electroconvulsions, which clearly indicates the difference in the design of experiments, hence, no wonder
about the difference in the finding.
Your correspondent
has further attributed to one of early
reports (8), that synthetic asarone is devoid of any eNS effect wnile isolated one shows pronounced effect".
No such finding has been reported in the paper and on the other hand it has been
shown in the same report that synthetic asarone significantly potentiated barbiturate induced hypnosis in mice. The conclusions drawn by Banerjce are therefore his own and he should know the
basis for arriving at such predictions.
No doubt synthetic asarone was found to be less potent
than asarone obtained from natural sources but this should not be surprising.
Substances prepared by different methodology are known to differ in activity.
Schlittler has reported that 17 desmethoxy deserpidine prepared by different procedures differed as regards the potency of its
sedative property (15).
68 Letter to the Editor
Janu~ry 1961
Ind. J. Physiol. & Pharrnacol
Banerjee's discovery of asarone as the first tranquillizer which could offer protection
to the extrapyramidal tract instead of producing parkinson's disease is very surprising. It is a
common knowledge that a drug which produces antitremorine effect may not necessarily be an
antiparkinsonian agent.
Potent antipsychotic and tranquillizing agent which produce parkinson like syndrome are also known to offer a remarkable protection against tremorine induced
tremors.
Patten et al (13) have shown that reserpine, and Leslie and Maxwell (11) have provided
evidence tha t nonantiparkinson
Phenothiazine derivatives like chlorpromazine, prochlorpera~i~~ and promazine inhibit the tremorine induced tremors in comparatively low doses.
Your corresponcent has not disclosed what was the starting material, what were the results
of his micro analysis and what modifications did he do in the method of Rao and Subramanium
(14) for isolating asarone ? The undersigned will aslo be interested to know about the nature of
1. R. spectrum of the asarone prepared by him, so that the readers may be able to judge its superimposable character.
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Banerjee's failure in recording the reduction in spontoneous motor activity in animals
treated with asarone could be attributed to the subjective nature of the procedure adopted by him
and also by Dandiya and Menon (6). Person to person variation is high when this technique is
adopted. Banerjee's contention that asarone in a dose of 3mg/ kg and IOmg/kg did not potentiate the pentobarbitone induced hypnosis, has certainly surprised us. I have repeated the experiment and to eliminate the ethyl alcohol and Tween 80 employed in making asarone solution
in our earlier srudies, solution of asarone was prepared by dissolving asarone in a few drops of
glacial acetic acid and making up the desired volume by adding requisite quantity of distilled
water. The method adopted was exactly identical with the method used by most of the workers
for preparing reserpine solution. The pH of the solution was 3.0 and this was used for all
experiments reported in this letter. Asarone 5mg/kg increased (P <'001) pentobarbital hypnosis
from 112. 9 (Control) to 202.7 minutes when groups of ten animals were employed for the experiment. Not only asarone caused hypothermia in mice (12) it brought about a similar action
in rats, when treated with 4mgj kg of this substance it lowered body temperature by 4.5°C in two
hours as against control 1.6°C when the experiment was done at an environmental temperature
of 16°C. It will be interesting to know at what room temperature Banerjee carried out these
experiments.
Even reserpine and chlorpromazine are known not to cause hypothermisa (3) at a
temperature of 30°C which is common in tropical countries.
Banerjee has further reported that asarone does not prevent fighting behaviour in mice
without even mentioning the strain used, the technique, the number of pairs employed and the
response obtained. Information on these points is of vital importance in the absence of which
any comment on his findings will be premature.
Banerjee's complaint regarding failure of asarone to block conditioned avoidance response (CAR) is most surprising. In our report, quoted by him (5) we have reported CAR aboli-
was
January
1968
Ind. J. Physiol. & Pharrnacol.
could offer
protection
's very sur prising. It is a
y not necessarily be an
nt which produce parkinst tremorine i.id uced
well(11) have provided
romazine, prochlorperatively low doses.
· , what were the results
f Rao and Subrarnani ID
ow about the nature
f
able to judge its super-
tor activity in animals
ocedure adopted by him
when this technique is
IOmg/kg did not potenIhave repeated the exp. 5 asarone solution
one in a few drops of
· quantity of distilled
by most of the workers
d this was used for all
pentobarbital hypnosis
employed for the expert about a similar action
rature by 4.5°C in two
· onmental temperature
jee carried out these
hypothermisa (3) at a
ting behaviour in mice
pairs employed and the
in the absence of which
Volume 12
Number 1
Is Asarone a Tranquilliser
69
shiug property in 3 out of 10 rats in a dose of 3mg/kg is not much different from Banerjee's 2
out of 12. I am only wondering as to how your correspondent thought fit to complain about it.
Whether asarone is devoid of any tranquillizing property can not be judged on the sketchy
evidence of this kind produced by Banerjee.
In this connection one may also refer to Chak
and Sharma's (2) report on asarone from CORI, Lucknow.
These authors have stated "Asarone
(3mgjkg ) is a central nervous system depressant resembling meprobamate and chlordiazepoxide
in its effect on conflict behaviour as it increases the number of shocks accepted by the animal
(rat) in conflict neurosis.
Since a number of drugs which increase the number of shocks taken
by an animal in conflict, have been used clinically to counteract anxiety, asarone may also be
cons'dered an antiauxiety agent". The same authors (2) have concluded that "asarone resembles
reserpine" as regards its antianxiety effect.
Before concluding r will like to emphasize that asarone has been shown to prolong hypnosis due to pentobarbital sodium, hexobarbital sodium and ethanol in mice (4) to protect Metrazol
induced convulsions and electroshock seizures while facilitating picrotoxin induced convulsions
in rats (4,16). It has also been shown to lower spontaneous activity, cause hypothermia
and
recuce anxiety as seen in conflict neurosis in choice discriminiation
test, as seen without dulling
preception in rats and reduced fighting behaviour in mice. (2,4,6.).
Besides bringing
about
such variety of pharmacologic actions in animals, asarone has the ability to potentiate the effects
of reserpine 011 conditioned avoidance response and electroconvulsions
in rats and on the fighting
response in mice (5). Asarone promptly counteracted the stimulation due to d - amphetamine,
LSD- 25, and iproniazid but only partially antagonized the effect of imipramine in rats and mice
(4, 17). It antagonised the hyperactivity due to mescaline in rats and also offered complete
protection to aggregated mice treated with toxic does of d- amphetamine.
In tremorine induced
temors in mice it was found to be inferior to atropine (7) .
It also prevented the depletion of
adrenal ascorbic acid in rats subjected to cold stress showing thereby that it is an agent specific
for counteracting stress (6). Whether a substance which has been shown to possess these aforesaid properties is a tranquillising agent or not can be judged by the readers and I will leave it to
them to judge the propriety of our exercise on determining its mechanism of action.
Banerjee
in his communication
(1) has obviously mixed up the term antipsychotic property with tranquillising property, which are fairly well differentiated in modern pharmacology literature (10).
It would not have been inappropriate
if Banerjee had also disclosed the identity of the
institution .where his studies were conducted while he was working as assistant research officer
of the I. C. M. R. In the absence of this information, are we to believe that studies were conduc
ted in the Department of Pharmacology,
University of Toronto from where his communication
was addressed ?
Dr. P. C. Oandiya
Professor of Pharmacolagy;
S. M. S. Medical College,
Jaipur, Rajasthan.
70
January 1968
Ind. J. Physiol. & Pharmacol.
Letter to the Editor
Ed
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