THE THERAPEUTICS OF 
METHYLENE BLUE, 
WITH SPECIAL REFERENCE TO ITS 
EMPLOYMENT IN URETHRITIS. 
BY 
WILLIAM J. ROBINSON, Ph.G., M. D. 
BEPBINTBD PROM THE 
York JHeDical journal 
for August 3, 1895. Reprinted from the New York Medical Journal 
for August 3, 1895. 
THE 
THERAPEUTICS OF METHYLENE BLUE, 
WITH SPECIAL REFERENCE TO 
ITS EMPLOYMENT IN URETHRITIS. 
By WILLIAM J. ROBINSON, Ph. G., M. D. 
In the New York Medical Journal for June 15, 1895, 
there appeared a report by Dr. Austin Flint of a case of 
Filaria sanguinis hominis successfully treated by methylene 
blue. At the conclusion he relates his experience with 
the use of the drug in gonorrhoea, in which disease it has 
in his hands proved highly successful. Though quite ex- 
tensively employed in some European countries, this drug 
has had a comparatively limited use in this country; but, 
taking into consideration the influence of Professor Flint's 
name, and the wide circle of readers of the Medical Jour- 
nal, it will not be surprising if many physicians are in- 
duced to try this drug in different diseases, and especially 
in gonorrhoea, which is often obstinate enough to baffle 
the skill and exhaust the patience of our best men, and it 
is for the specific purpose of emphatically warning the 
profession against the employment of this drug that I am 
induced to give my experience with it. 
Copyright, 1895, by D. Appleton and Company; 2 
THE THERAPEUTICS OF METHYLENE BLUE. 
Before I do so, I want it to be distinctly understood 
that all reports about methylene blue-mine, which follow 
below, included-must be taken with some mental reserva- 
tion, cum grano salts ; the simple but important reason 
being that methylene blue varies so widely in composition, 
and other aniline compounds are so frequently substituted 
for it, that we can seldom be sure as to what particular 
substance is under consideration-to what compound to put 
the blame or credit for certain beneficial or disastrous 
effects. Why it should be so with methylene blue more 
than with any other chemical I do not know, but it is a 
fact, as will be seen presently. 
Methylene blue is, as is well known, the hydrochloride 
of tetra-methyl-thionine, but, as found in commerce, it is 
frequently a double chloride of zinc and tetra-methyl-thio- 
nine, besides containing as impurities lead and arsenic, as 
can be easily demonstrated by making a solution, filtering, 
and passing a stream of sulphureted hydrogen, when the 
metals will be precipitated as sulphides. As regards sub- 
stitution, the substance I have found most frequently sub- 
stituted for methylene blue, and vice versa, is methyl violet 
(blue pyoctanin). Some time ago a friend was treating a 
case of carcinoma mamrme by painting around with a solu- 
tion of supposed methylene blue and was very gratified at 
the results. It afterward proved that he had been using- 
right along a solution of methyl violet, and only a few 
days ago 1 ordered a two per-cent, solution of pyoctanin 
blue for a case of varicose ulcers and methylene blue was 
dispensed instead, the druggist explaining to me that he 
was sure it meant the same thing. 
In the Medical Record for August 26, 1893, Dr. A. 
Rose reports some cases of diphtheria treated very success- 
fully with methylene blue, concluding with the remarkable 
statement that methylene violet was dispensed on his pre- THE THERAPEUTICS OF METHYLENE BLUE. 
3 
scriptions instead of methylene blue, and that to his 
knowledge such errors have occurred elsewhere. To what 
remedy then is credit due, to methylene blue or violet ? 
With regard to my experience with methylene blue in 
gonorrhoea, although not large, it has been sufficient to 
convince me not only of its utter worthlessness, but of its 
positive injuriousness. Of the eleven cases of specific ure- 
thritis that I treated with that drug, four were chronic, of 
from six months' to three years' duration, and in those 
four the drug did not exert the least influence for good; in 
two of them all the symptoms became aggravated, the dis- 
charge increasing, the urine assuming a burning charac- 
ter, etc. 
Of the seven acute cases one was markedly benefited. 
This patient presented himself for treatment ten hours 
after exposure and two hours after noticing a slight dis- 
charge. He was given a saturated solution of boric acid 
as an injection and methylene blue 0T2 three times a day. 
On the sixth day the discharge was completely stopped. 
In two other cases it seemed to act beneficially, but, as it 
was given in conjunction with other antiblennorrhagics, 
the results are, of course, doubtful. 
In the other four cases the effects were perfectly disas- 
trous, assuming in two such an alarming aspect that it 
seems to me worth while to relate them in detail : 
Case I.-A. M. C., aged twenty-five years; occupation, engi- 
neer; second attack; noticed discharge February 7th; presented 
himself for treatment on the 14th. Discharge profuse, but 
other symptoms rather mild. Ordered a mild injection of sul- 
phocarbolate of zinc and hydrastis and methylene-blue capsules, 
0'1, four times a day. On the night following, about 1 a. m., I 
was waked up by my patient, who complained of very severe 
vesical tenesmus and absolute inability to urinate. lie told me 
he felt bad right after taking the first capsule, but kept on. 
From 2 p. m. he passed no urine, and the pressure in the blad- 4 
THE THERAPEUTICS OK METHYLENE BLUE. 
der was becoming unbearable. I administered a large dose of 
potassium bromide and applied hot compresses to the perinaaum, 
but these means being ineffective, I was obliged to catheterize. 
The tenesmus and soreness in the urethral canal persisted for 
two or three days. Under antiblennorrhagics, with salol and 
mild antiseptic injections, the cure was complete and rapid. 
Case II.-S. B., twenty-eight years of age; a tall, powerful 
man; occupation, iceman; moderate drinker; has slight gastric 
catarrh; several previous attacks; noticed discharge March 
25th. Treated himself with strong solution of zinc sulphate and 
carbolic acid and with patent nostrums. All the symptoms be- 
coming aggravated, he applied for treatment April 7th. I pre- 
scribed a sedative alkaline mixture and an injection of aqueous 
hydrastis with boric acid. He returned on the 14th and I gave 
him the following prescription : 
Methylene blue (Merck) 4'0 
Pulv. opii 0-5 
Pulv. myristicae 12'0 
M., ft. pulv., div. in caps, gelat. no. xxx. 
Sig.: Capiat capsulam unam quater in die. 
He took one that afternoon and one in the evening; after the 
latter he got a severe headache and passed a restless night. 
Early next morning he took another capsule and went on his 
route with his ice wagon. The beadache became worse- 
" splitting," as he said-and he complained of dizziness and pain 
in his stomach. Not thinking of the possibility of there being 
any connection between his symptoms and the capsules, he took 
another one at twelve o'clock. His headache and pain after 
that became excruciating, and he fainted on the wagon. The 
man who was with him took him home and he was put to bed. 
For about an hour he remained dazed, mildly delirious, show- 
ing signs of suffering intense pain in the stomach and in the 
bladder. He tried several times to urinate, but failed. At last 
he passed about two ounces of dark blue, almost black, urine, 
on seeing which rare phenomenon his relatives became fright- 
ened and sent for me. When I came in he bad an attack of 
vomiting which relieved him. His skin was covered with cold 
perspiration, pulse rapid and feeble, temperature 99° F. Under THE THERAPEUTICS OF METHYLENE BLUE. 
5 
Dover's powder and phenacetine he perspired freely, and his 
headache, which was still violent, became relieved. A Sitz 
bath and two to three doses of potassium citrate with tincture 
of hyoscyamus enabled him to pass a large quantity of urine 
(blue-colored) with very little pain. For two days he was un- 
able to get out of bed, so great was his exhaustion. A slight 
vesical tenesmus lasted for about three days, and a dull gnaw- 
ing pain at the pit of the stomach for about eight days. His 
urethritis was cured in about three weeks under appropriate 
treatment. 
This settled the fate of methylene blue in my practice 
-for internal use, at any rate. 
My conclusions are as follows: If we see a case of spe- 
cific urethritis in a very early stage-the first day-then 
the use of methylene blue, by its direct action on the gono- 
cocci, may do good, though we run the risk of strangury 
and general toxic manifestations. But as soon as the gon- 
ococci have penetrated beneath the epithelial layer of the 
urethral mucosa then methylene blue can do nothing or harm. 
I have used it in three cases of intermittent fever with 
fair results, but its action is certainly much inferior to that 
of quinine and arsenic. My general conclusion, therefore, 
coincides with that of Laveran, that used internally methylene 
blue is good only for one purpose-to color the urine blue. 
It is an excellent coloring agent, though, for the plasmodia 
malariae and the gonococci Neisseri, and is useful when em- 
ployed externally in cancerous and tuberculous affections. 
It is undoubtedly very pleasant to be in a position to re- 
port brilliant successes and cures from a new remedy, but 
it is certainly just as useful to show the reverse side of the 
medal, and thus save our fellow-practitioners many failures 
and our patients much unnecessary suffering. 
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