ATROPINE. 
ITS PHYSIOLOGICAL ACTION, AND 
ITS USE IN TETANUS, WITH 
EXPERIMENTS. 
Communicated for the Boston Medical and Surgical Journal 
BY 
ROBERT AMORY, A.M., M.D. 
BOSTON: 
DAVID CLAPP & SON, PKINTEKS, 
1869. ATROPINE; ITS PHYSIOLOGICAL ACTION, 
AND ITS USE IN TETANUS. 
Having had an opportunity of trying two 
well-known and violent poisons in some 
cases of tetanus, I thought it might be in- 
teresting to publish some account of the 
effects of these remedies, and must ask for a 
brief space in your Journal. 
Two forms of tetanus are recognized, the 
idiopathic and traumatic ; names which in- 
dicate their supposed origin, but which re- 
veal our ignorance of the pathological con- 
ditions under which they may occur. Teta- 
nus may follow a slight injury, or some 
more serious wound. Dr, Dewees, in the 
Medical Gazette, considers * “ that in idio- 
pathic tetanus a very frequent first step is 
sudden arrest of violent perspiration ; and 
that certain reflective acts may be thrown 
upon some disordered or impressible cere- 
bro-spinal centre, causing convulsive mus- 
* Dec., 1862. 4 
cular manifestations ; ” and goes on to show 
“ how these repressed excreta act specifi- 
cally, abrogating or over-exciting the ner- 
vous functions, thus producing all sorts of 
incurrent disorders.5’ If this be so, the 
same effects which cause the disease, unless 
modified by some remedial or restraining 
action, tend to increase its manifestations. 
In accordance with these principles veteri- 
nary surgeons try by tremendous doses of 
aloes and other purgatives to relieve the 
system of excreta, and allow the animal to 
recover. Sometimes this treatment meets 
with success, especially in the form called 
idiopathic, but, generally, the prognosis is 
made (and correctly) that the animal will 
die. 
The animals generally die from asphyxia 
or exhaustion, and in frightful convulsions. 
It would seem from what is known of the 
pathological condition produced by tetanus, 
that the sympathetic nervous system is in 
an abnormal state, that of continued excita- 
bility, in which there is spasmodic contrac- 
tion of the capillaries as well as of the vol- 
untary and involuntary muscular system. 
The pathological investigations made af- 
ter death from tetanus, throw but little 5 
light upon our knowledge of the disease. 
The results are very often contradictory or 
doubtful, and have often been explained by 
a reference to the position of the body ex- 
amined, in which extravasated blood was 
shown to gravitate towards certain points. 
Chloroform has a restraininginfluence upon 
the tetanic spasms, but they recur as soon 
as the inhalation ceases. Before speaking 
of Belladonna as a remedy, I should like to 
notice some of its physiological effects. 
Atropine seems to be poisonous to all 
animals, provided it is received and retained 
in a sufficient quantity in the blood. Her- 
bivorous animals appear to eliminate the 
poison very rapidly, and both belladonna 
and atropine, in doses sufficient to kill seve- 
ral men, have been borne by goats, rabbits* 
guinea pigs and sparrows, with no incon- 
venient symptoms beyond dilatation of the 
pupil and diarrhoea. In carnivorous ani- 
mals, however, its poisonous effects are 
very manifest, even in minute doses. Two 
milligrammes of a grain) produce cere- 
bral trouble and serious accidents in man. 
If, however, fatal poisoning by this drug 
occurs, it follows very soon after its admin- 6 
istration, as the drug is very rapidly elimi- 
nated. 
Slight doses accelerate the capillary cir- 
culation, reducing the calibre of the arte- 
rioles, to 1-3 or 1-2 (by micrometer) their 
normal size. This retraction of the blood- 
vessels is not uniform, but the walls of the 
arterioles become unevenly contracted in 
undulations.* The diminution of calibre 
coincides with the acceleration of the cir- 
culation. Ilaydenf has concluded that this 
constriction is due to reflex action. For in 
cutting the integument of a frog’s leg this 
same phenomenon occurs. The sciatic 
nerve contains some filaments of the sym- 
pathetic system also, so that we must not 
be surprised to find that the constriction 
produced by this operation is not as marked 
as that caused by the atropine. Hayden 
also notices the coincidence of accelerated 
circulation with the constriction. These ef- 
fects on the circulation continue but a short 
time, and the arteries soon return to their 
primitive condition. The veins do not di- 
minish in volume. 
* Wharton Jones, Med. Times and Gazette, 1857, p. 27. 
t Dublin Quarterly Jour, of Med. Science, Aug. 1862. 7 
If, however, the dose be larger, the cir- 
culation slackens, and then completely 
stops. All the vessels are gorged with 
stagnant blood, a perfect hypereemia re- 
sults. This stasis commences in the ven- 
ules and then ensues in the capillaries and 
arterioles. The blood stops in the artery 
only after the stasis occurs in the capilla- 
ries. These same effects occur, also, when 
the drug is applied to a portion of the cir- 
culation under microscopical observation. 
The effect of the smaller dose is exciting, 
and its local application seems painful to 
the frog. In the denuded skin of man the 
pain is compared to that produced by a hot 
iron. 
In larger doses it seems to paralyze the 
vaso-motor system ; the flesh has a blood- 
red appearance, and with the microscope is 
seen to be in a state of hypereemia. These 
peculiarities have been also observed in the 
mesentery of the rat, and in the ear of rab- 
bits. Meuriot * would then consider atro- 
pine as a vasculo-cardiac agent, and to his 
memoir, mainly, I am indebted for much of 
my knowledge of its action. 
* Paris, 1868. 8 
With regard to its qualities as an anaes- 
thetic, Meuriot affirms that superficial neu- 
ralgia derives much benefit from atropine 
if applied topically. In small doses, how- 
ever, exhibited by the stomach, I know of 
three cases of nervous headache which have 
been often and decidedly relieved by bella- 
donna. In fact, homoeopathists prescribe 
their sugar-plums of belladonna for all head- 
aches of this kind, and their success is noto- 
rious. 
The inconvenience of hypodermic appli- 
cations of atropine is the severe pain caused 
by its contact; which, as I have already 
said, has been compared to that caused by 
a hot iron. This may persist for two or 
three days, and is supposed to be owing to 
the trouble in the capillary circulation of 
the skin. We see the same conditions in 
severe chilblains. This drug never destroys 
Sensibility, but may induce analgesia. 
Nerves in contact with atropine preserve 
their excitability, and the contact of the 
electrodes causes contractions, reflex move- 
ments, and cries. 
In frogs peripheric sensibility is dimin- 
ished, but this is not the case with other 
animals experimented upon. 9 
Its action upon the spinal cord as com- 
pared with strychnine and bromide of po- 
tassium is peculiar. 
Strychnine produces an exaltation or ex- 
aggeration of the excito-motory functions 
dependent upon this central organ. The 
bromide diminishes the activity of these 
functions, whilst atropine has an interme- 
diate action, but with a tendency to their 
increase rather than their diminution. The 
effects are in proportion to the dose admin- 
istered, large doses tending to a stasis, the 
smaller to a diminution of blood in the spi- 
nal meninges and nerve-substance. 
It would seem strange (if the foregoing 
summary of the physiological action of bel- 
ladonna be correct) that this drug should 
be recommended in tetanus. If in this 
disease there is congestion of the nervous 
centres or peripheries, we shall be increas- 
ing rather than diminishing the determina- 
tion of blood to the capillaries and to the 
spinal cord, unless we should use much care 
in apportioning the dose ; as we have seen 
that it is only in small quantity that atro- 
pine tends to diminish the amount of blood 
in the spinal meninges and nerve-substance. 
But it would be a very difficult matter to 10 
determine an amount which in every person 
should produce the same effect. It would 
be only by carefully watching that we could 
produce a modification of the tetanic spasms 
and keep the action of the drug within the 
limit. Thus, much caution would be re- 
quired in the application of the drug to 
those cases in which we wished to produce 
oligsemia or hypermmia in the tissues of 
the body, 
Oligeemia of the brain resulting from a 
deficiency of blood-globules acts in the 
same way as a section of the spinal cord, or 
an exaggeration of the excito-motor power, 
and therefore we must beware, lest in avoid- 
ing Scylla we fall into Charybdis. 
It may be said, that the physiological ac- 
tion of drugs upon man and animals is not 
subject to the same laws, and, frequently, 
does not produce the same effects. This 
cannot be exactly true with this drug, as 
its action, so far as at present known, is the 
same upon man and animals ; provided that 
the drug has entered the venous circulation 
in a form sufficiently concentrated. Some 
animals can so rapidly eliminate it, that 
only a quantity insufficient to produce tox- 
ical effects, is present in the capillary cir- 11 
culation at one time, and hence their appa- 
rent immunity to its baneful action.* That 
the urine of a goat fed with belladonna 
leaves was injected into the stomach of a 
dog with fatal results, and that his urine 
caused dilatation of the pupil in another dog, 
is a very curious fact; and shows that a 
dose which a dog cannot quickly enough 
eliminate may remain in a goat’s bladder, 
unabsorbed into the capillary circulation. 
If the urethra of the goat had been tied up, 
imbibition of the poison and prevention of 
its elimination would probably have pro- 
duced a different result. 
f The action upon the pupil results from a 
destruction of the excitability of the fifth pair 
of nerves. Electrization, and the action of 
certain excitors of muscular contractility 
(myotiques) upon atropinized eyes seem to 
show that the sphincter of the iris will pre- 
serve its power of contracting. But the 
feeble action that is observed from the ex- 
hibition of atropine after the section of the 
great sympathetic, and the different results 
obtained from electrization of eyes under 
* N. Y. Medical Journal, 1868, p. 278. 
f Meuriot, sur la Belladonne, Paris, 1868, p. 137. 12 
the influence of atropine, depending1 on the 
destruction or integrity of the sympathetic 
nerve, seem to indicate that this drug has 
an exciting action upon the terminations of 
the sympathetic. The demonstration is also 
given in the effects of atropine on eyes of 
which the motor occularis communis is 
completely paralyzed, and experimentally 
on animals when the sphincter iris is de- 
stroyed. Belladonna is not a hypnotic but 
possibly a stupefying narcotic. In small 
doses it induces agitation and insomnia, in 
large doses stupor, in intermediate doses 
dreams and general tremblings. 
The effect upon the temperature has been 
found by numerous observers to be an in- 
crease of from 1-2 to 8-10 of a degree centi- 
grade. 
Atropine causes dryness of the skin and 
of the mucous surfaces, probably from a re- 
absorption of the liquids on account of the 
increased rapidity of the circulating cur- 
rent, Thirst from atropinization may be 
thus accounted for. The local action of the 
drug upon the mouth produces salivation. 
As the peripheric sensibility is also dimin- 
ished, the secretions are decreased. In this 
state acetic acid placed upon the tongue 
does hot salivate. 13 
Small doses augment the pressure of the 
blood in the kidneys, large doses diminish 
the pressure, and thus, according to Ber- 
nard,* in the former case we obtain diuresis, 
and in the latter suppression of urine. 
M. Behier f recommends for tetanus sub- 
cutaneous injections of the valerianate of 
atropia along the nape of the neck, and 
gives the following formula : 
R. Atropim valerianatis, .30 = grs. v. 
Aquse, 30.00 = §i. 
Of this 5 drops to be injected every two 
hours. Pescheux (Verneuil) reports a case 
of tetanus relieved by subcutaneous injec- 
tions of atropine sol. 1-100. Three-fourths 
of the syringe of Pravaz (3'grammes) were 
injected, in doses of 10 drops at a time. 
Symptoms of atropic poisoning (slight) oc- 
curred, and the tetanus disappeared. 
ATROPINE AS A REMEDY FOR TETANUS. 
On the 2d of April, 1868, I received a 
request from Dr. Stickney to visit a horse 
suffering from an attack of lockjaw, in a 
stable in my vicinity. On inquiry I found 
* Lecons sur les Liquides de I’Organisme, 1859, tome 
11. p. 155. 
f Diet, de Med. et Chir. Paris, Bailliere et fils, 1866,, 
tome IV. p. 86. 14 
that the animal had been ailing for a few 
days, and that sulphur in large quantity 
had been given by the hostler in charge. 
He had not eaten anything since Friday, 
and had had but little discharge from the 
bowels or bladder. The facial muscles and 
those of the neck were very rigid, though 
elsewhere they were but slightly if at all 
affected. The animal could not open his 
mouth, nor could it be forced open. Dr. S. 
had ordered him small doses of prussic 
acid by the rectum every two hours. 
Three days afterward I was told that Dr. 
Stickney had given me the liberty of re- 
sorting to any expedient that might be sug- 
gested, and I went again to see the horse. 
He was respiring rapidly and was in much 
distress, and the spasmodic contractions 
were more extended and severe. The eyes 
were half closed. 
It is unnecessary to give more details. 
The peculiarities of tetanus are well known 
and easily understood from the descriptions 
recorded in standard works. The disease 
had increased very rapidly during the 
twenty-four hours, and now there was no 
muscle which was not tense in a greater or 
less degree. Several methods occurred to 
my mind to try as alleviations of the 15 
spasms, as a cure was now out of the ques- 
tion. I had in a previous case tried hy- 
drocyanic acid unsuccessfully. Strychnine 
and electricity I thought of, especially the 
latter. However, upon reflection I consid- 
ered it advisable to ask Prof. Brown-Se- 
quard, what drug it would be advantageous 
to experiment with. Several drugs were 
discussed, but the one he preferred was 
atropine, and, at his advice, I publish the 
record of the experiment. I procured one- 
sixth of a grain of the sulphate of atropia, 
which I dissolved in two drachms of water. 
At I P.M., on the same day, I injected 
subcutaneously, according to the advice of 
this eminent physiologist, this solution in 
three different doses (with ten minutes in- 
terval between each) under the fore-shoul- 
der. The animal was under the influence 
of chloroform for ten minutes before the 
first injection was made, in order to prevent 
any serious agitation. 
In half an hour after the last injection he 
discharged a moderate quantity of urine ; 
and, as he appeared much easier, I left him 
for an hour. On my return I found him 
still more comfortable, and again three 
hours after the hostler told me that he had 
been lying down and had got up again ; the 16 
muscular spasm was a little reduced, espe- 
cially in the hinder part of the body. 
On the next morning', the man showed 
me about a hatful! of soft faeces that the 
horse had passed during the night, and said 
that the bedding was well soaked with his 
urine. I then obtained one grain more of 
the sulphate of atropia, which I dissolved 
in eight pints of water. I directed that one 
pint of this solution should be injected into 
the rectum every hour, and that between 
the first and second doses they should inject 
some milk and water. The first injection 
was made at 1 P.M. At 8 o’clock the man 
came down and said that they had suc- 
ceeded in opening the horse’s mouth, that 
he was in a great sweat, and that he had 
been trying to eat his bedding ; he wished 
to know what he might give him to eat. I 
directed first that the medicine should be 
omitted ; second, that they should boil some 
carrots and squeeze their juice into a pail 
of water, put in this a handfull of bran 
and a wine-glassful of alcohol; that while 
this was preparing they should give him 
some water if he could drink it. In an 
hour afterwards I found him bathed in a 
profuse sweat, the muscles surprisingly re- 
laxed, and the animal drinking water of his 17 
own accord from a pail. His mouth was 
partially open, and the eyelids so drawn up 
that with difficulty could I see the iris. He 
had drunk some of the liquid food, pre- 
pared as directed, but did not like it, 
probably on account of the alcohol. So 
I was ordering some other mixture when 
Dr. Stickney appeared. He was much sur- 
prised on seeing the change in the horse, 
and we were both sanguine (too much so as 
it afterwards proved) of the animal’s recov- 
ery. He said that he had never seen so sud- 
den a change in tetanus in a horse. I asked 
him to prescribe the diet, and soon we left. 
On my return, three hours after, the animal 
had passed a large amount of faeces, and 
much urine. His mouth was still open, 
and the muscles much relaxed, but not so 
much as on my previous examination. I 
therefore ordered another pint of the diluted 
medicine to be placed in his pail of water. 
He had just drunk a quantity of oatmeal 
gruel, and had lain down and got up again 
several times. Still, as the spasms were 
apparently stronger, I considered it im- 
portant to give another dose of atropine. 
Two pints had been injected, making a 
quarter of a grain of atropine introduced 
into the rectum. At 9 o’clock the next 18 
morning- (Wednesday, Tth) I found on in- 
quiry that the horse was dead. On an in- 
vestigation I found that at 5 o’clock a noise 
of kicking was heard in his stall, and the 
man on going down found the animal throw- 
ing his head round while lying on his side, 
kicking violently with all four feet, and 
bathed in sweat. Evidently, from his de- 
scription, the horse was in a convulsion, 
which lasted twenty minutes or so, after 
which the animal expired. He said that 
the muscles were not very stiff, not so much 
so as before the atropine had been given, 
A natural question is suggested, whether 
this was a case of traumatic tetanus ? There 
was no proof that it was. The horse.had 
been lying idle all winter in a cellar stable, 
and had been shod four weeks before his 
attack. He had been exposed in a pad- 
dock to our last severe snow storm, and 
shortly after began to ail. 
ATROPLE VALERIANAS. 
June 21th, 1868.—Tetanus. Colt 1 year 
old. This disease manifested itself June 
26th, P.M., two weeks ago, after castration. 
This morning the long muscles of the 
neck are distinctly marked by tension of their 
fibres. The membrana nictitans is drawn 19 
over the eye when a hand is placed near 
his head. As in the last case there is hy- 
peresthesia of the skin. The hind legs ap- 
pear stiff, though the individual muscles are 
not particularly tense. The wound in the 
scrotum appears well. There is no swell- 
ing of the sheath or neighboring parts. 
There is a slight running of serum from the 
scrotum down the legs (this I understand 
is perfectly normal, and another healthy colt, 
castrated at the same time, shows the same 
phenomenon. Respiration appears easy, 
and the animal can chew grass slowly, and 
drink water, though the latter is swallowed 
more noisily and with more difficulty than 
is usual with horses. Faeces have passed 
recently and appear moist. The man in 
charge says that he has passed urine, but of 
this I have my doubts. The man is not to 
be relied on, as he is apt to speak as he 
thinks he is desired. 
I administered subcutaneously a solution 
of atropiae valerian., containing a little less 
than 1-24 gr. The puncture apparently 
gave a good deal of pain, though he did not 
seem to mind the injection of the fluid. He 
afterwards ate and drank as before the in- 
jection. The pupil was not dilated half an 
hour after the injection, nor was there any 20 
amelioration. I left directions for 1-50 gr. 
to be injected per rectum two hours after, 
and 1-24 gr. two hours after that, and another 
dose at 9 or 10 P.M. 
The directions were carried out and a 
large amount of the drug was administered 
per rectum. 
The physiological action upon the iris 
was very marked, butthe disease had gained 
ground and the animal died three days af- 
ter I first saw him. The colt had taken 
2| grs. of the drug in all. In this last case 
no effect upon the tetanic symptoms was 
observed. The disease increased, in spite 
of the drug, and this even while the system 
was showing the physiological action of this 
drug. 
Perhaps it may be of interest to the read- 
ers of this article to give the conclusions 
regarding the action of Belladonna arrived 
at by M. Meuriot in the brochure before al- 
luded to: 
I. “Atropine is the active principle of 
belladonna, and assumes all the properties 
of this solanum,* 
* In this family are also included tobacco, henbane, 
datura, stramonium and the dulcamara; as also the to- 
mato, egg-plant, potato and capsicum. Prof. A. Gray, 
p. 456. 21 
11. “The intensity of its actionvaries with 
the species of animals. Herbivora are less 
sensible to its action than the Carnivora. 
In man its poisonous action is the most vio- 
lent ; but no animal is exempt. 
111. “ Its action also varies with the dose 
employed ; for small doses accelerate the 
heart’s pulsation and augment the vascular 
tension ; poisonous doses diminish the ten- 
sion and modify the cardiac pulsations. 
IY. “ Belladonna is a vasculo-cardiac poi- 
son, in the classification of M. See. Its ac- 
tion produces especially the innervation of 
the heart and of the vessels. 
Y. “The varied phenomena produced by 
Atropine depend mostly upon its primordial 
and elective action, or are due to the elimi- 
nation of the poison. 
VI. “Atropine acts upon the heart through 
the pneumogastric nerve, whose peripheral 
extremities are paralyzed. It augments 
the frequency of the cardiac pulsations. 
YII. “In a small dose it augments the 
tonicity of the vascular muscles ; in a poi- 
sonous dose it diminishes, and even de- 
stroys this ; whence the application of Bel- 
ladonna to epilepsy, in which the access 
seems to be due to modifications of cerebral 
circulation. 22 
YIII. “ The variations of the arterial 
tension are subordinate to the state of exci- 
tation or paralysis of the muscular coat of 
the vessels. 
IX. “In small doses atropine accelerates 
the respiration ; in poisonous doses it di- 
minishes its frequency. 
“ The acceleration of these movements 
depends upon the excitation of the respira- 
tory centres ; the consecutive retardation, 
upon a paralysis of the extremities of the 
vagi nerves ; whence its application in the 
treatment of asthma. 
X. “ xVtropine in a therapeutical dose, in- 
creases the activity of the excito-motory 
functions of the spinal cord. 
“ In a poisonous dose it exaggerates the 
reflex power till it may produce convulsions. 
XI. “ Atropine always produces agita- 
tion, insomnia, delirium, and in a poisonous 
dose, coma ; it is not at all a narcotic. 
XII. " Atropine is eliminated by the kid- 
neys, by all the mucous surfaces, and some- 
times by the skin of man. Its elimination 
is always rapid ; so that its action is of 
short duration. 
XIII. “ The effects due to elimination 
are numerous, viz. : redness of the mucous 
Surfaces and of the skin, frequent desire of 23 
micturition ; colic; anal and vesical tenes- 
mus ; profuse sweat, diarrhoea, &c, 
XIV. "The redness and dryness of the 
mucous membrane explains aphonia, dys- 
phagia, dysuria, &c. 
XV. “Xot only are all the secretions of 
the mucous membrane diminished, but there 
may be also, on account of the activity of 
the circulation, a rapid reabsorption of all 
the liquids which have exuded from mucous 
surfaces or from wounds ; whence its ad- 
vantage in exaggerated secretions, and its 
effect upon coughs, &c. 
XVI. “ Atropine, applied locally to the 
tissues, produces an activity of the capil- 
lary circulation, and, in a considerable dose, 
true hypersemia and sanguineous stasis. 
“ Angina and erythema produced by bel- 
ladonna are analogous to the inflammatory 
process. 
XVII. “The modification of the urinary 
secretions are dependent upon the varia- 
tions of the arterial tension. 
XVIII. “ Belladonna is not a paralyzing 
agent to the smooth muscular fibres; it 
produces no phenomena of paralysis except 
in a very powerful dose, and in these cases 
it follows exaggerated contractions; thus 
it is of benefit in incontinence of urine and 24 
of the faeces, in paralysis of the bladder, in 
constipation, irreducible hernias, &c. 
XIX. “ Atropine has no elective action 
upon the sensitive nerves. Its local appli- 
cation is always followed by acute and per- 
sistent pain. Atropine acts only upon 
nerves in a state of hyperaesthesia and often 
determines analgesia, but it should be ap- 
plied directly upon the seat of pain (les 
nerfs affectes). 
XX. “ Small doses of atropine augment, 
toxical doses diminish, the temperature. 
XXI. “ Atropine, especially, possesses 
the property of causing dilatation of the pu- 
pil, and this is its most constant and per- 
sistent effect. 
“It paralyzes the terminal branches of 
the third pair of nerves ; this is the only 
fact well shown by experimental physiolo- 
gy, in the study of the hyoscyamus also. 
(Gubler). 
“ To this paralysis of the ciliary branches 
of the nervous motor ocularis communis is 
attached the paralysis of the muscle of ac- 
commodation. 
XXII. “ Certain experiments and several 
considerations that have been made public 
by the author, tend to show some exciting 
action upon the sympathetic nerve or upon 
the dilatateur. However, a more vigorous 
demonstration is still essential/’ * 
* Meuriot, op. cit. p. 138, et seq.