November 23, 1872.] THE PHARMACEUTICAL JOURNAL AND TRANSACTIONS. 
405 
newly acquired atoms when treated with alkalies, hut 
remains pentatomic even when subjected to attacks 
more violent than any to which it could he exposed in 
the system. 
I he type of the natural alkaloids is that of ammonia, 
hut certain varieties of constitution are met with. In 
ammonia, the nitrogen is united to three equivalents of 
hydrogen. Now, one or two or three of these equiva¬ 
lents may he replaced by one or more radicals, and in 
this way we have amine, imine, and nitrile bases. Thus, 
one equivalent of hydrogen is replaced hy C H 3 in the 
( (CH 3 )' 
amine base, methylamia, N < II ; two equivalents hy 
t H 
the diatomic radical (C 8 H 14 ) ,/ , in the imine base, normal 
coma, N j w ; and three equivalents, hy the 
same diatomic radical, and hy C Id 3 , in the nitrile base, 
methyl-conia, N j > or, to take another example 
of a nitrile base, by one equivalent of the triatomic radical 
(C 2l H .->2 NO,)in strychnia, N 3 (C 21 H 22 NO,) w . 
These various bases are distinguished from the bases de¬ 
rived from them in which nitrogen is stably pentatomic 
(called ammonium bases) by certain chemical characters 
common to them all. Their salts, for instance, are de¬ 
composed by caustic potash, so that the base is set free, 
and water and a salt of potassium formed; and a simi¬ 
lar effect is produced by moist oxide of silver. The 
salts of the ammonium bases, however, are not acted 
upon by caustic potash, and, when treated with moist 
oxide of silver, a hydrated oxide of the ammonium base 
(in which nitrogen remains pentatomic) is formed, and 
the acid unites with the silver. 
The powerful decomposition action which caustic 
potash is able to exert, does not, therefore, change the 
chemical constitution of these ammonium bases. It, in¬ 
deed, has no effect upon their salts ; and even when 
these salts are treated with moist oxide of silver the 
characteristic pentatomicity of their nitrogen is retained. 
In thn living body, they cannot possibly be subjected 
to the influence of such powerfully decomposing agents ; 
and hence, by studying their action, and comparing it 
wuth that of the nitrile or other base from which they 
are derived, the relationship between physiological action 
and a certain form of chemical constitution may be dis¬ 
covered. 
^ It was owing to this consideration that Ur. Crum 
Brown and Dr. Fraser resolved to examine the action of 
a number of the ammonium bases derived from the 
vegetable alkaloids. Their experiments were made with 
the methyl, and, in a few instances, the ethyl, deriva¬ 
tives. of strychnia, brucia, thebaia, codeia, morphia, 
nicotia, atropia, and conia, and more especially with 
their iodides and sulphates. The results obtained may, 
perhaps, bo best illustrated by describing, with a little 
detail, several of their experiments with iodide and sul¬ 
phate of methyl-strychnium. 
It is well known that strychnia acts on the living 
economy in a distinctively defined and characteristic 
manner, and that it is one of the most active of poisons. 
When administered subcutaneously, doses varying from 
one-twentieth to one-fiftieth of a grain produced in 
rabbits the most violent tetanic convulsions, and in a few 
minutes killed the animal. Few poisons have been more 
carefully studied, and it is now almost undoubtedly 
established that the phenomena produced by strychnia 
are due to a localization of its action on the spinal 
cord. 
I he effects of iodide of methyl-strychnium were first 
examined by subcutaneous injection. It was adminis¬ 
tered as a fine powder suspended in warm distilled 
water, in which menstruum it is but sparingly soluble, 
though more so than in water at the ordinary tempera¬ 
ture. In this way, by a series of progressively increas¬ 
ing doses, it was found that as much as twelve grains 
could be given to a rabbit, weighing throe pounds, 
without any effect whatever. Fifteen grains, however, 
produced serious symptoms, though followed by re¬ 
covery ; and death was caused by the administration of 
twenty grains. In none of the experiments, not even in 
the fatal cases, were the symptoms those of strychnia- 
poison ; no starts nor spasms occurred, nor did stimula¬ 
tion give evidence of the slightest increase of reflex 
activity. In fact, a condition exactly the reverse of that 
produced by strychnia was caused by iodide of methyl- 
strychnium. In place of violent spasmodic convulsions 
and muscular rigidity, the appearances were those of 
paralysis with a perfectly flaccid condition of all the 
muscles. The limbs of the animal first yielded; its 
head gradually sank until it rested on the floor; by- 
and-by, it lay in a perfectly relaxed condition ; and 
when death occurred, it was due to stoppage of the 
respiratory movements. In the necropsies, further evi¬ 
dence was obtained to distinguish the effects of iodide 
of methyl-strychnium from those of strychnia. The 
heart was found acting with nearly its normal rapidity; 
the spinal motor nerves wore either paralysed, or nearly 
so; and, in place of the early or almost immediate oc¬ 
currence of rigor mortis that follows the action of strych¬ 
nia, the muscles continued flaccid, contractile, and alka¬ 
line for many hours. 
Administered internally, suspended and dissolved in 
warm distilled water, no effect was produced, although 
as much as thirty grains was given at one time. One- 
tenth of a grain of strychnia, however, also adminis¬ 
tered by the stomach, quickly produced violent tetanic 
convulsions, and in a few minutes killed the animal. 
Sulphate of methyl-strychnium being a very soluble 
salt, it was anticipated that it would act with much 
greater activity than the iodide, and experiment con¬ 
firmed this anticipation. One grain dissolved in water 
and injected under the skin of a rabbit caused its death 
in eighteen minutes. Half a grain, however, produced 
no marked effect. When eight-tenths of a grain were 
similarly administered, symptoms of a most serious cha¬ 
racter were produced, but death did not result. Some 
days afterwards, one-twentieth of a grain of strychnia, 
dissolved in very dilute sulphuric acid, was administered 
to this rabbit by subcutaneous injection; and it pro¬ 
duced symptoms of strychnia action, followed by death 
fifteen minutes after the injection. Eight-tenths of a 
grain of sulphate of methyl-strychnium contain about 
six-tenths of a grain of strychnia; the effect of con¬ 
verting this nitrile base into an ammonium base by 
adding to it sulphate of methyl had been, therefore, to 
reduce its poisonous activity at least twelve times. 
The symptoms produced by sulphate of methyl-strych¬ 
nium were the same as those produced by the corre¬ 
sponding iodide, and suggested a close resemblance be¬ 
tween its action and that of curari (wourali)—a resem¬ 
blance, indeed, which had previously been pointed out 
by Professor Schroff, of Vienna. Dr. Brown and Dr. 
Fraser accordingly extended their research for the pur¬ 
pose of studying the exact causation of the paralysis, and 
found that in experiments where iodide of methyl- 
strychnium was substituted for sulphate, the results were 
the same, and that their mode of action is identical with 
that of curara. This result is an extremely curious and 
interesting one. It is difficult to imagine a more decided 
modification in the action o any substance than is pro¬ 
duced by the change of chemical constitution resulting 
from the addition of iodide or sulphate of methyl to 
strychnia. The striking- characteristic of the action of 
strychnia is the great and uncontrollable activity of the 
muscular system ; that of curara, of iodide and sulphate 
of methyl-strychnium, and, as was also found, of other 
similarly modified alkaloids, is the flaccid and motionless 
condition caused by the impossibility of exciting mus¬ 
cular action through the nervous system. So opposite 
are their effects, that many physiologists look upon 
curara as a powerful counter-agent to strychnia, while 
