A COMPARATIVE STUDY OF THE PHYSIO- 
LOGICAL ACTIONS OF BRUCINE 
AND STRYCHNINE. 
BY L 
EDWARD T. REICHERT, M.D., 
PROFESSOR OF PHYSIOLOGY, UNIVERSITY OF PENNSYLVANIA. 
FROM 
THE M EDICAL, NEWS, 
April 8, 1893. [Reprinted from The Medical News, April 8, 1893.] 
A COMPARATIVE STUDY OF THE PHYSIO- 
LOGICAL ACTIONS OF BRUCINE 
AND STRYCHNINE., 
By EDWARD T. REICHERT, M.D., 
PROFESSOR OF PHYSIOLOGY, UNIVERSITY OF PENNSYLVANIA. 
But little experimental and clinical investiga- 
tion has been made with brucine, its more potent 
and cheaper sister-alkaloid, strychnine, having over- 
shadowed it. However, what records we do possess 
indicate, for the most part, that these substances 
exert essentially the same influences upon the organ- 
ism, the differences being in degree rather than in 
kind. One serious difficulty met in the studies of 
the actions of brucine has been that the preparations 
commonly found in the market are, to a greater or 
less extent, contaminated with strychnine, usually to 
such a degree that whatever actions might have 
been exerted by brucine seemed entirely superseded 
by the more powerful influences of the strychnine. 
Thus, in the elaborate experimental study of bru- 
cine made by Wintzenried (.Tnaug. Dissertation, 
Geneva, 1882) the results so closely resembled those 
caused by strychnine that it is still believed by many 
leading pharmacologists that the phenomena were 
due to the contaminating strychnine. 
There are, however, on record certain statements 
which lead to the belief that brucine does possess 2 
physiologic properties entirely distinct from those of 
strychnine. Thus, Mays, in observations on frogs and 
man (Therapeutic Gazette, June, 1885), found that 
pure brucine acts as a strong local anesthetic, and 
Robins (Philadelphia Medical Times, 1879, p. 228) 
also noted that this substance depresses the sensory 
nerves. Mays asserts that brucine induces in the 
frog a short period of motor weakness, or even 
paralysis, in the posterior extremities preceding the 
period of convulsions. There is also evidence to 
indicate that brucine is of the nature of a motor 
paralyzant (Klapp, Journ. Nerv. and Ment. Disease, 
1878, p. 619 ; Wintzenried, loc. cit.; Robins, loc. 
cit.'). Finally, Brunton states (Jonrn. Chem. Society, 
1885, p. 143) that brucine is innocuous when taken 
by the stomach. 
While we thus have reasons for the belief that 
there are important dissimilarities in the physio- 
logic actions of these two alkaloids, it is not possi- 
ble in the light of present knowledge to say to what 
extent they are due to variations in the purity of the 
drug used, to dosage, to the differences in the species 
of animals employed, etc. 
The object of the present inquiry has been to 
determine to what degree important physiologic 
actions of brucine and strychnine are related. To 
that end essentially the same line of investigation 
was carried out as in my recent elaborate research 
with strychnine (Therapeutic Gazette, March, 
April, May, and June, 1892), which will form the 
basis of comparison with the results of the present 
investigation. Over 100 experiments were made, 
about one-fourth being upon dogs, and the re- 3 
mainder upon frogs. The brucine was made by- 
Merck, a standard preparation, guaranteed to be 
absolutely free from strychnine. The specimen was 
subjected in our laboratory to the most rigid testing, 
and the results fully substantiate Merck’s claim. 
In the frog, after minunal lethal doses, no marked 
differences are observed in the results caused by 
brucine or strychnine, other than that the former 
is less prompt in action, that the motor disturb- 
ances caused by it are of less violence, and that it 
affects the volitional centers sooner and more pow- 
erfully. In the brucinized frog a failure of volun- 
tary motion and an increase of reflex excitability 
are simultaneously developed, the former progress- 
ing usually with greater rapidity than the latter, so 
that volitional movement is, as a rule, lost before the 
exaltation of reflexes is sufficient to provoke con- 
vulsions. This loss of voluntary motion may be 
mistaken, as by Mays, for a general condition of 
motor paralysis. In the strychninized frog voluntary 
motion is also lost, but never until after the onset of 
convulsions. The differences, therefore, are not in 
kind, but in degree ; brucine acting with less vigor 
as a convulsant, and with greater power upon the 
cerebrum. After the administration of much larger 
doses absolutely no differences are detected in the 
phenomena exhibited by the two sets of frogs. 
Brucine being absorbed with less readiness than 
strychnine is consequently less prompt in its effects. 
The belief of Robins and Mays that brucine de- 
presses the sensory r.erves, leading to the conclusion 
that this action is unlike any of strychnine, is true 
in fact, but not in deduction. Neither exerts any 4 
influence on the sensory nerves in minimal lethal 
doses, but both depress and finally paralyze these 
nerves when the poisons are given in great excess. 
In the mammal, as in the frog, the only important 
differences in the phenomena noted are those of 
degree, and not of kind. 
The statement made by Brunton (loc. cit.) that 
brucine is innocuous when administered by the 
stomach is not supported by sufficient evidence to 
give it any value, and, besides, is contradicted by the 
results of my own experiments. Brunton’s conclu- 
sion is based upon the result of a single and by no 
means satisfactory experiment made upon a rat, to 
which he gave o.i gram of pure brucine, mixed 
with suet, so that the animal ate it readily. The 
rat was not affected by the dose, although another, to 
which the same quantity was administered by injec- 
tion into the abdominal cavity, fell into convulsions 
within three minutes and died. 
The records of one of my experiments will be suf- 
ficient to prove that absorption does take place 
through the stomach, but with much less rapidity 
than in the case of strychnine: 
Experiment.—Dog; weight, 8617 kilos. 9.30. 
Gave per stomach through a catheter, 0.18 gram of 
brucine. 9.40. Acts as though he heard flies flying 
about his head; otherwise no apparent change. 
10.30. An occasional twitch or jerk of the skin, or in 
one of the legs. 10.35. Twitchings and jerkings more 
pronounced and observed in the skin, ears, head, and 
extremities; reflex activity greatly increased, a 
slight touch causing considerable muscular disturb- 
ance; there is pronounced muscular stiffness, espe- 
cially when any movement is attempted ; respiration 5 
is very quiet and 24 per minute. 11.40. Vomits; 
respiration imreased in frequency; and panting. 
11.55. Salivation; marked rigidity; great hyper- 
esthesia ; a breath of air induces a condition of 
rigidity bordering on tetanus, 11.57. Tetanus, 
followed by slow, deep respirations, which grad- 
ually pass to those of a frequent and panting 
character. 12.20. Quiet and sickly; respirations, 
140; profuse salivation; occasional slight spasms 
of the body and legs. 12.26. Opisthotonos; failure 
of respiration ; heart continued beating for several 
minutes after the cessation of respiration. 
The non-toxic result of Brunton’s experiment is 
doubtless to be attributed to the extremely slow 
absorption of the poison, owing to its admixture 
with suet. 
Whatever dissimilarities may exist in the actions 
of brucine and strychnine are best elicited by gen- 
eral and special studies, such as were pursued in the 
investigations with strychnine already alluded to. 
When a 1 per cent, solution of brucine is injected 
into the external jugular vein of a dog, the general 
results which follow are not apparently in any way 
distinguishable from those resulting from the injec- 
tion of strychnine. There occurs within a few 
moments a condition of muscular excitement, which 
rapidly passes into one of violent tetanic convul- 
sions, and death ensues immediately from an arrest 
of re piration, or, after a time, from exhaustion. 
Should, however, forced artificial respiration be 
practised at and after the time of the convulsive 
seizures, the spasms gradually disappear, the general 
condition of the animal becomes in most respects 
the same as just before the convulsions, and the 6 
effects of the poison slowly wear away. But if with 
the appearance of the convulsions the injection of 
brucine or strychnine is continued, the tetanus 
grows less and less violent, voluntary motion is lost, 
reflex excitability rapidly disappears, the spasms give 
place to somewhat rhythmical jerkings of the mus- 
cles (choreic in character), and these to twitch- 
ings, which, in turn, are lost, and the animal lies 
absolutely motionless, save for the movements due 
to artificial respiration and the heart-beats. The 
circulation and heat processes, and other important 
functions, generally remain in good condition, and 
the dog may be kept alive for hours, if not days, 
thus paralyzed, if brucine or strychnine be from time 
to time injected. 
The state of absolute muscular quiet is not, as a 
rule, of long duration, unless the dose has been un- 
necessarily large, for usually, in the course of fifteen 
or twenty minutes, fibrillary twitchings reappear, 
invariably in the inverse order of their disappear- 
ance from the various parts. These movements 
become more and more marked, gradually passing 
to violent rhythmical jerkings, and finally to clonic 
convulsions. 
These remarkable changes from the normal state 
to violent tetanus, and finally to complete motor 
paralysis, cccur with such rapidity that the latter 
stage may be reached within three minutes. 
The quantity of brucine, when intra-venously 
injected, necessary to cause death, is about 0.008 
gram to the kilo of body-weight; and of strychnine 
about 0.0002 gram. The dose required to pro- 
duce absolute motor quiet is for both poisons about 7 
the same, being from 0.015 to 0.020 gram per kilo 
of body-weight; strychnine being, perhaps, a little 
more powerful. Thus, it will be observed that while 
strychnine is greatly more powerful as a convulsant, 
it is as a paralyzant of practically the same toxicity 
as brucine. 
The relative toxicity of strychnine, compared with 
that of brucine, is, according to Magendie, 12:1, 
and according to Andral 24:1, and according to 
my experiments about 40:1 for the dog and about 
50:1 for the frog. The differences given in the 
proportions of Magendie, Andral, and myself, re- 
spectively, are doubtless owing largely, if not solely, 
to the degree of purity of the brucine employed. 
These figures by no means indicate, as before 
stated, the relative potencies of the two poisons 
upon different parts of the organism. As is well 
known, both substances cause death by asphyxia, 
which results from the violent convulsive seizures; 
but, as I have pointed out in my memoir on strych- 
nine, the virulence of strychnine as a convulsant in 
relation to its other powers is so extraordinary that a 
fatal result ensues long before many other important 
actions are developed. It is only by the prevention 
of the continuance of the convulsive seizures, the 
use of artificial respiration, and the administration 
of comparatively enormous doses of the drug, 
that its full train of action is obtained. This 
statement holds good for brucine ; consequently, 
the figures indicating that strychnine is so many 
times more powerful than brucine signify that it 
is that many times more potent as a convulsant; and 
they must not be taken as an expression of the rela- 8 
tive intensities of the actions of the drugs on the 
various parts of the economy. In some respects 
brucine is of equal toxic value in its action ; in 
other respects, of greater value ; and in still other 
respects, of less value. 
A careful comparison of the results of the detailed 
studies made with these alkaloids shows so. few and 
unimportant differences that the conclusions arrived 
at from the study of strychnine are applicable to 
brucine, with slight additions and modifications. 
In the following summary where differences exist 
they are distinctly stated; otherwise it may be 
considered that the actions and effects are iden- 
tical. 
1. The minimum lethal dose of brucine for the 
dog, when intra-venously injected, is about 0.008 
gram to the kilo of body-weight, and of strychnine 
about 0.0002 gram, the relation being 1140. In the 
frog the minimum lethal dose of brucine is about 
0.1 gram, and of strychnine about 0.002 to the kilo 
of body-weight, when subcutaneously injected. 
2. Doses of from 0.015 t0 0.020 gram to the kilo 
intra-venously injected cause a condition of absolute 
muscular quiet, and by means of artificial respira- 
tion the animal may be kept alive in excellent gen- 
eral condition. 
3. Quantities in excess of 0.1 gram to the kilo 
may be intra-venously injected in divided doses 
without causing death, provided that artificial res- 
piration be employed. 
4. The toxic actions of brucine and strychnine 
are so directed to the motor center in the spinal 
cord that the minimum fatal dose is exceedingly 9 
small, owing to the production of asphyxia or to 
exhaustion by the violence and persistence of the 
tetanic seizures. Should artificial respiration be 
maintained, about 500 times the minimal lethal 
dose may be injected without an immediately fatal 
result. 
5. By a proper regulation of the size of the dose 
and the method of administration, the stage of 
excitement may be prolonged over an almost in- 
definite period, or may be so brief as to last for but 
a few seconds. 
6. During the stage of excitement the following 
actions and effects are observed : 
a. The motor disturbances and convulsions are of 
spinal origin. 
b. The sensory nerves and muscles are unaffected. 
c. The motor nerves, after the onset and continu- 
ance of convulsions, become depressed from over- 
work. 
d. The pulse-rate is first lessened in frequency, then 
increased, and finally diminished. The first effect 
is due to a stimulation of the cardio-inhibitory ap- 
paratus, the second to its depression, and the last 
to a depression of the excito-motor ganglion, or 
automatic-motor ganglion in the heart. 
e. The arterial pressure is primarily diminished, 
then greatly increased, and at last diminished. The 
first effect is due to some obscure action on the vaso- 
motor centers in the medulla oblongata; the rise of 
pressure to a stimulation of the vaso constrictor cen- 
ters in the same part; and the final fall, to a de- 
pression of the heart and vasomotor centers. In 
curarized animals the rise of pressure due to stimu- 10 
lation of the vasomotor centers is relatively and 
absolutely greater than in the non-curarized animal. 
f The respiration-rate is not specifically affected, 
unless it be in the nature of a decrease, or during 
the period of convulsions, when it maybe decidedly 
increased. 
g. The bodily temperature is increased. 
7. During the stage of paralysis the following are 
noted : 
a. The muscles are not in the least affected 
unless after enormously excessive doses. 
b. The sensory nerves are inexcitable to strong 
electric currents. 
c. When the motor nerves are subjected to a pow- 
erful faradic current, spasm of the muscles supplied 
no longer occurs, although the nerves transmit im- 
pulses from the nerve-centers—irritability is lost, 
but conductivity remains. 
d. The pulse-rate is reduced, but the height of the 
curves is increased ; the first effect being due to a 
depression of the motor, ganglia in the heart, and 
the second effect to the .greater filling of the 
viscus with blood, and perhaps to a direct stimu- 
lation of the heart. The cardio-inhibitory fibers 
are paralyzed, but no increase in the frequency 
of the pulse-rate is observed, owing to the pre- 
dominance of the depressant action on the heart- 
ganglia. Stimulation of the vagi causes smaller 
pulse-curves, and a slight increase in the frequency 
of the beats. 
e. The arterial pressure is increased, unless the 
dose has been greatly in excess, when it is dimin- 
ished. The increase is due to a stimulation of the 11 
vasomotor centers in the medulla oblongata, and the 
decrease to a depression of the heart and to vaso- 
motor paralysis. The increase of pressure is greater 
and more persistent in curarized animals. In non- 
curarized animals the pressure sinks below the 
normal immediately after the tetanic paroxysms, but 
in those curarized this depression is less marked. 
Asphyxia and electric stimulation of a sensory 
nerve fail to cause a rise of pressure, as in the normal 
animal; on the other hand, asphyxia is always 
accompanied by a fall. 
f The hemoglobin is in some way affected so 
that it cannot be oxygenated to the normal degree, 
although the spectroscope reveals nothing but 
oxyhemoglobin.' 
g. The temperature may be increased or decreased 
by brucine, but is always increased by strjchnine. 
Cocaine is unable to cause its characteristic increase 
of heat-production and temperature, as in the normal 
animal. Apparently, both str)chnine and biucine 
paralyze the accelerator thermogenetic centers, and 
leave intact the automatic thermogenetic centers. 
h. The paralytic condition caused by strychnine 
and brucine closely resembles that produced by 
curare, but is in many ways entirely distinct. 
8. The chief differences in the physiologic proper- 
ties of brucine and strychnine are as follows : 
a. Brucine is less rapidly absorbed than strych- 
nine, and, as a consequence, is less prompt in its 
actions. 
b. Brucine is from forty to fifty times less powerful 
as a convulsant, and, therefore, proportionately 
less fatal. 12 
c. Brucine acts relatively more powerfully on the 
volitional centers in the frog than as a motor ex- 
citant, with the effect oftentimes of causing in these 
animals a loss of volitional movement preceding the 
stage of convulsions. In mammals, however, it 
does not seem that either poison ever destroys voli- 
tion before the appearance of convulsions. 
d. In excessive doses brucine is more poisonous 
to the sensory nerves than is strychnine. 
e. During the last stage of the poisoning the 
action of brucine on bodily temperature is uncer- 
tain, while that of strychnine is positive. Brucine 
is, ultimately, a stronger depressant to the heart, and 
after enormous doses more toxic to the muscles. 
9. The green frog (Rana esculenta) is somewhat 
more susceptible to brucine than the spotted frog 
(Rana temporaria). The same difference I have 
noted with strychnine. 
The results of this research render it obvious that 
the physiologic actions of brucine and strychnine 
are essentially identical, the differences being prac- 
tically solely in degree, and not in kind. This, 
together with the fact that the convulsant action of 
brucine is in the mammal about forty times less than 
that of strychnine, indicates that brucine will prove 
not only a safer drug, but of infinitely greater value 
as a general therapeutic agent. 
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