150 Phenothiazine—A Remarkably Efficient Anthelmintic
In common with other anthelmintics its mode of action remains something
of a mystery, and its addition to the short list of really effective medicinal
parasiticides cannot be regarded as the outcome of a scientific understanding
of the principles by which their action is governed. The use of phenothiazine
as an anthelmintic can be traced back through a series of rational trials to the
first observation on its insecticidal properties, made by the workers in the
United States Bureau of Chemistry and Soils, who on account of the lack of
information at present available on the correlations between chemical struc-
ture and parasiticidal action were forced to carry out their investigations by a
method of trial and error. As each new anthelmintic substance is found,
however, fresh opportunity for study is provided, and it is not improbable that
an investigation of some of the peculiar points concerning phenothiazine treat-
ment may help to explain the mode of anthelmintic action.
The most outstanding peculiarity concerns the requirement for a large
dose of the drug. Although it is practically insoluble in water we were able to
demonstrate a definite parasiticidal action on adult worms in vitro, and a very
marked toxic action on the eggs and preinfective larval stages of strongyloid
worms in faeces, operating down to a dilution of about one part of the drug in
8.000 parts of faeces. (It was interesting to note, however, that Muellerius
larvae were quite unaffected.) Knipling (1938) obtained similar results in
his observations on the control of the hornfly in cattle when he found that the
phenothiazine passing through the intestine of cattle for three days after
dosing was sufficient to inhibit the development of hornfly larvae in the
faeces.
These observations are suggestive of an extremely potent action of this
drug since the actual amount in solution must be very small indeed, and it is
surprising to find that rather large doses are requisite for full anthelmintic
action. Swales (1939) considered it necessary to give 20 or 30 grammes to a
sheep and Swanson et al. (1940) gave up to 30 grammes to a pig. Although
our observations indicate the adequacy of a smaller dose it is nevertheless
much greater than the tests in vitro would seem to indicate. Our results
suggest that a dose of 5 grammes produces a good anthelmintic effect in sheep,
and that 10 grammes approaches to the maximum anthelmintic effect. Ten
grammes to a horse was clearly inadequate but 20 grammes, in some instances,
proved to be 100 per cent efficient, although in others its action was much less
marked ; 30 grammes however produced the maximum result in almost every
instance and it may be concluded from our results that for ordinary purposes,
10 grammes (0.3 grammes per kilo) is adequate for a sheep and 30 grammes
(0.06 grammes per kilo) for a horse.
An interesting observation in connection with dosage was made at the
Zoological Gardens, London, by G. M. Vevers who, in a private communica-
tion, reported the expulsion of large numbers of Enterobius from a gorilla as
the result of the administration of only 0. 5 grammes of phenothiazine.
There is, therefore, seen to be something unusual about the anthelmintic
action of this drug in that the dose generally required, having regard to the
insolubility of the drug, seems to be unnecessarily large. In an endeavour to
explain this peculiarity we considered the possibility of the formation within
the animal body, of some second substance, of much greater anthelmintic