149 
1919-20.] The Harmala Alkaloids in Malaria. 
Harmine is about twice as toxic as quinine for laboratory mammals, 
and therefore could probably be given to man in about half the dosage of 
quinine. The dose employed of harmine, 3 grains per day, would, unless 
it was proportionately much more toxic than quinine to the malarial para- 
site, almost certainly be insufficient to cut short acute attacks. It would 
be interesting to know whether larger doses of harmine would be more 
successful for this purpose. 
In the three cases of relapsing malaria it seemed to act much better 
than quinine. In these cases quinine had been given over long periods and 
had failed to prevent relapses. It would be remarkable if the relapses 
ceased in each of the only three cases tried precisely upon the administration 
of harmine, without the result being in part at least due to the action of 
this alkaloid. The results so far obtained are, however, sufficiently en- 
couraging to warrant further trial of harmaline and harmine in malaria 
and other protozoal diseases. The plant from which they are obtained is 
very common and widely distributed, and if it proved of therapeutic value 
the alkaloids could be obtained from it cheaply and in quantity. While 
many more experiments would be required to delimit the value of these 
harmala alkaloids in malaria, perhaps the results so far obtained and here 
recorded will induce others, who may have the opportunity, to endeavour 
to obtain more decisive results based upon wider experience. 
Summary of Results. 
Harmaline has been tried in experimental trypanosomiasis in rats. 
While it has a toxic action on the trypanosomes in vitro, it was not found 
to have any curative effect on the disease in the doses given. 
Harmaline has been tried in acute malaria. In half the cases it caused 
disappearance of the parasites from the peripheral blood, fall of temperature, 
and relief of symptoms. In the other half of the cases it failed to check 
the disease, though quinine subsequently did. In the doses given it is 
inferior to quinine for acute malaria. 
Harmine has been tried both in acute and in relapsing malaria. It 
failed to cut short acute attacks. In three cases of relapsing malaria 
it proved remarkably successful, preventing the recurrence of attacks when 
long-continued quinine administration had failed to do so. 
Both alkaloids could with safety be given in much larger doses, and 
probably better results could be obtained in this way, both in acute and in 
relapsing malaria. 
{Issued separately October 13, 1920.) 
