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Phenothiazine—A Remarkably Efficient Anthelmintic
administered 30 grammes of the phenothiazine-containing faeces to a second
goat heavily infected with parasitic worms. A filtrate of a watery solution of
another 30 grammes of the same faeces was administered to a third goat, also
heavily infected with parasitic worms. Observations on the egg output of the
two goats that received the " medicated " faeces failed, however, to reveal
any effect on the parasitic worms.
Following this observation we carried out two trials with oxidation pro-
ducts of phenothiazine produced within the animal body. The first of these
was thionol* which is the red dye that causes the red coloration of the urine in
animals treated with phenothiazine and is the oxidation product of leuco¬
thionol which, after exposure of small portions of tissue to the air, is seen to be
present in almost every part of the body of an animal that has received a large
dose of phenothiazine. These substances form the reversible oxidation-
reduction system thionol—leucothionol, similar to that of methylene blue—
leucomethylene blue, well known to workers on clean milk. The second sub-
stance was phenothiazone which according to Gersdorff and Claborn (1938) is
extremely toxic to goldfish.
Both of these substances were tested in doses of 0.25 grammes and 2
grammes in goats heavily infected with parasitic worms but without producing
any anthelmintic effect whatsoever.
Nothing, therefore, was done to elucidate the reason for the necessity of
giving much more phenothiazine than is required to produce a saturated solu-
tion in the contents of the intestinal tract in order to produce anthelmintic
acton,+but it seems not unlikely that some factor of importance for the under-
standing of the action of phenothiazine, and, possibly for the understanding
of anthelmintic action in general, lies hidden in this one particular problem.
SPECIFICITY OF ANTHELMINTIC ACTION.
Our own results show that phenothiazine is particularly lethal to strongy-
loid worms, ‡ its most pronounced and certain action being exerted on those in
the large intestine of the horse, where, in adequate dosage, it can be relied
upon to eradicate all of the adult forms. The species of Strongylus, however,
appear to be slightly more resistant than are the smaller " red-worms," S.
vulgaris being the most resistant of all.
Second only in efficiency is its action on the tricho-strongylid worms in the
fourth stomach of sheep where, in adequate dosage, it has proved to be 100
per cent efficient on several occasions ; this high efficiency is, however, less
reliable than on the red-worms in horses. Species of Ostertagia respond
* The thionol and phenothiazone was kindly prepared for our use by Dr. Sexton of
the Imperial Chemical Industries Laboratories at Blackley.
† The theory on which we are working at the present time is that it is necessary to
maintain a saturated or nearly saturated solution of phenothiazine in the intestine for
some considerable time in order to secure anthelmintic action and that to insure against
the exhaustion of the reservoir of phenothiazine in the rumen, or in the large intestine
in equines) it is necessary to give a large dose. In vitro observations appear to support
this view.
‡ An interesting exception has been mentioned by Manson-Bahr, who, in a private
communication, reported having found phenothiazine to be relatively ineffective against
Ancyclostoma although very effective against some other worms in the human being.