STUDIES ON ALSTONIA SCHOLARIS

  I. A PRELIMINARY INVESTIGATION ON THE UTILIZATION OF THE BARK OF
              ALSTONIA SCHOLARIS AS A REMEDY AGAINST PROTOZOAL
                                             INFECTIONS IN ANIMALS

By K. VENKATACHALAM and M. R. SUBRAMANIA SASTRY, Research Unit, Medical College, Madras

                                   (Received for publication on 23 March 1943)

                                                 (With Plate XXIII)

ALSTONIA SCHOLARIS belonging to the
natural order Apocyanaceae is commercially
known as Dita bark. It is also known as Chatin
in Bengali, Saptaparna in Sanskrit, Satwin in
Hindi and Marathi and Ezhilaippalai in Tamil.

It is a tall, ever-green and a highly ornamental
tree, widely cultivated throughout India and found
in the sub-Himalayan tracts from the Jumna
eastwards ascending to 3,000 ft. in Bengal,
Burma and south India. Its bark is reported to
be a valuable remedy as an antiperiodic in the
treatment of malaria. This reported property of
the bark led to the belief that it may prove useful
in the treatment of similar protozoal infections
in animals. The possibility of thus securing a
local remedy for such protozoal infections induced
the authors to undertake the investigation on
this plant. Efforts were therefore made:

    (1)  to isolate the active principle,
    (2)  to find out whether it acts as a proto-
          plasmic poison, and
    (3)  to study the pharmacological actions of
          the alkaloid on the circulatory system.

Echitamine hydrochloride was isolated in
the pure form. Its chemical properties tallied
with those already described by previous workers,
[Goodson and Henry, 1925].

Studies were first made to find out whether it
acts as a protoplasmic poison. Its action was
compared with that of emetine hydrochloride,
quinine hydrochloride, hydrargyri perchloride and
acidum carbolicum, which are known protoplasmic
poisons. A culture of paramacea in hay infusion
was used for the experiment. The results of
the experiment indicated that even 1 per cent
solution of echitamine hydrochloride did not
affect the motility of the organisms in 16 minutes,
whereas 0.2 per cent solution of emetine hydro-
chloride and 0.5 per cent solution of quinine hy-
drochloride killed them in 16 minutes, while 0.1
per cent solution of mercury perchloride and 0.5
per cent solution of carbolic acid killed them with-
in a minute. It is, therefore, clear that echita-
mine hydrochloride does not act as a protoplasmic
poison in vitro and this is in conformity with the
observations of Henry [1939] 'that the alkaloid
does not exhibit any anti-malarial action in
laboratory tests'. It is, however, possible that
it may destroy the protozoal organisms in vivo
by means of tissue reactions.

A dose of 5 to 10 mg. of the alkaloid injected
intravenously to anaesthetized animals produced
a marked fall in blood pressure, followed by slow
recovery (Plate XXIII, fig. 1). Several dogs, cats
and monkeys were experimented upon, and this
action was found to be constant.

After severing both the vagii, an injection of
echitamine produced the same fall in blood pres-
sure indicating that the action is not through the
vagal centre (Plate XXIII, fig. 2). The vagal
terminals were subsequently paralyzed with atro-
pine injections containing 0.165 mg. to 0.65 mg.
according to the weight of the animal, given in
divided doses. The paralysis was ensured by
ascertaining the absence of any reaction on blood
pressure to electric stimulus to the vagus. Echita-
mine hydrochloride injected when the vagal
terminals were completely paralyzed still pro-
duced the fall in blood pressure, indicating that
the action is not through the terminals also
(Plate XXIII, fig. 3). The findings of White as
quoted by Henry [1939] ' that the alkaloidal
sulphate induces a fall in blood pressure in the
anaesthetized cat which is unaffected by atropine '
are confirmed by the above experiments.

Raymond-Hamet as quoted by Henry [1939]
found' that this alkaloid exerted no sympatheco-
lytic action in producing the fall of blood pressure.
But no one seems to have attempted to study the
action of the alkaloid on blood pressure, after
removing the sympathetic vaso-constrictors. The
effects produced by the drug, after paralyzing the
sympathetic vaso-constrictors with ergotoxine,
were therefore studied by us. An injection of
echitamine after ergotoxine was found, con-
trary to expectation, to produce a definite and
prolonged rise in blood pressure instead of a fall
(Plate XXIII, fig. 4). Several experiments were
made on anaesthetized cats, dogs and monkeys, and
the same effect was observed in all the cases. The
cause for this rise of blood pressure when the vaso-
constrictors are paralyzed and even when adrena-
line produces a fall in blood pressure will form the
subject of a subsequent paper.

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