THE 
MODERN HYPNOTICS. 
BY 
HENRY M- WETHERILL, Jr,, M. D., Ph. G., 
Philadelphia, Pa. 
FROM 
American Journal of Ensamtg, 
July, 1889. 
UTICA, N. Y. THE MODERN HYPNOTICS. 
BY HEN BY M. WETHEBILL, JB., M. D., PH. G., 
Assistant Physician at the Pennsylvania Hospital for the Insane, Philadelphia. 
The past few years have witnessed the birth of a multitude of 
new chemical compounds, most of which have well-marked physio- 
logical action, and are mainly divisible into three classes—those 
derivatives of coal-tar whose principal effects are to cause a lower- 
ing of the animal temperature and antisepsis; those of the ether 
series of compounds which have an anaesthetic and hypnotic action 
when inhaled or otherwise introduced into the system; and a third 
important and very different group of complex organic composi- 
tion, which are the so-called active principles of vegetable life. It 
is with some members of the two latter groups that we will deal 
in the present inquiry. 
The remarkable impetus received by organic chemistry through 
the activity of the modern, and especially of the German chemists, 
is responsible for the appearance of a new remedy, frequently an 
hypnotic, every few months; taxing the attention of the physician 
to become familiar with even its name and physical properties, to 
say nothing of the time and application necessary to investigate its 
individual merits. 
The profession of medicine, and especially those of it who daily 
minister to the requirements of the insane, has been upon the 
outlook for the ideal hypnotic, but it is unreasonable to hope to 
find in a single one all the properties requisite to overcome the 
many and varied causes of insomnia. It is an humiliating ad- 
mission, (which has truth for its justification) that our present 
knowledge of therapeutics is largely empirical, and it is thus of 
necessity that we turn, in an emergency in treatment, to a list of 
drugs having supposed identical, or closely similar physiological 
action. This fact must form the chief excuse for the search for 
and the employment of so great a number of more or less hypnotic 
substances, and it is a common experience to be disappointed in a 
given case in the action of a remedy which may have answered a 
useful purpose in another case as nearly similar in conditions and 
indications as possible. It should always be the aim of the prac- 
titioner to have a scientific motive for every dose prescribed, as it 
is far safer and more honest to leave Nature to struggle single 
handed with the malady than to medicate haphazard. The habit 2 
of routine administration of drugs is one into which the asylum 
physician is especially prone to fall, and it is all the more difficult 
to avoid, because the temptation to do so is strong, amid the 
harrassing small details daily recurring in hospital life. It has been 
recently demonstrated by one of our staff (Dr. E. N. Brush) that 
there are many instances of insomnia in hospital as well as in 
private practice which neither require nor should receive strictly 
medical treatment, but which were relievable by a course of baths,, 
massage and special nourishment in the evening, yet the fact 
remains that the large majority of the insomnious insane require 
relief by the administration of sedatives or hypnotics, and the 
problem confronts us—1st. What is the nature and physiological 
action of these recently introduced medicines? 2d. What is their 
relative hypnotic power? 3d. What special indications should 
guide us in the selection of any one from the others, in pre- 
scribing ? 
In order to attempt the solution of these in an intelligible man- 
ner, let us take up, as briefly as possible, the consideration of the 
most important of these new substances seriatim. 
HYOSCYAMINE AND ITS SULPHATE. 
This member of the vegetable group cannot be classed as strictly 
a new remedy, as a substance which he named hyoscyamine was 
extracted from the fresh seeds of H. niger by Brandes, in 1820; 
but as it remained for years a mere chemical curiosity, and had 
since appeared on the market at intervals in such diverse forms 
and potencies as to lead to general distrust, it may be considered 
therapeutically new since its revival in a reliable form by the 
German chemists, led by E. Merck of Darmstadt. 
Prior to this the alkaloid was represented in trade by clear, 
purified resins, and by soft, waxy extractives in which could be 
found, by the microscope, a few warty crystals, and these prepara- 
tions varied in activity from utter inertness to the proportionate 
strength of a recent, well prepared solid extract of the fresh 
German leaves. 
In 1833, Geiger and Hesse succeeded in producing a similar 
substance having rather more potency, but as little reliability. 
Kemper in 1866 improved a little upon the efforts of his prede- 
cessors, but it was not until 1871 that Hohn succeeded in freeing 
it, in the form of small, white crystals, from the inert mass of 
resin, fixed oil and extractives that had held it captive previously. 3 
Thibault, in 1875, crystallized hyoscyamine in a state of purity 
from a chloroformic solution of mixed resins and waxy, oily by- 
products. The fresh leaves contain more hyoscyamine than either 
the roots or the seeds of II. niger. Ladenbnrg has recently 
studied carefully the several sources of the alkaloids of the natural 
order solanaceae, of which the three important are atropia, hyoscy- 
amine and hyoscine, all of which are represented by the formula 
0|y, H33, N03, but differ radically in physical and physiological 
properties. Of these hyoscyamine is found in atropa belladonna, 
in datura stramonium, in hyoscyamus niger and in duboisia 
myoporoides, while hyoscine is found only in hyoscyamus niger. 
It having been observed that in working upon belladonna root, 
according to the manner of operating, sometimes more hyoscya- 
mine and sometimes more atropia was obtained, experiments have 
been made that led to the following conclusions: 1st. That in 
belladonna root of good quality scarcely any atropia exists 
already formed, but only hyoscyamine. 2d. That from any bella- 
donna roots, according to the manner of operating, it is possible 
to obtain, at will, either hyoscyamine, or so-called “ heavy atropia,” 
or a mixture of the two. 
When oxidized, say by hydrochloric acid, hyoscine splits into 
tropine and tropic acid, and hyoscyamine similarly treated breaks 
up into several analagous substances. The pure alkaloid hyoscy- 
amine, as is the case with all such derivatives, is difficult of solution 
in water, but the chemists present a sulphate of hyoscyamine in 
two forms: one crystallized in yellowish-white masses and scales; 
the other in an apparently amorphous form, purely white, in 
which it resembles small masses of carbonate of magnesium. If 
this latter be examined under the microscope, it will be found to be 
minutely crystalline. These two sulphates are in every way 
identical: the former having been a result of the spontaneous 
evaporation of a solution, the latter the result of precipitation. 
These two salts, as they are at present offered by E. Merck, we 
have found uniformly reliable, in about equal doses: the so-called 
amorphous being a little the stronger, grain for grain, as it con- 
tained less water of crystallization, and they proved equally and 
readily soluble in cold water and in alcohol, pure, or variously 
diluted, forming reasonably permanent solutions. So much for its 
physical properties. 
Our experience in the use of hyoscyamine sulphate dates from 
the year 1883, and has continued, more or less, to the present time. 
Series of careful observations were made several times daily upon 4 
groups of selected cases of insanity by the writer, a portion of 
whose results and tables was published in 1885. The doses 
ranged from grain l-60th, which is a proper initial quantity, to 
grain l-12th. Two lines of investigation were pursued: one to 
test the hypnotic power of the drug, the other its supposed 
sedative action upon conditions of motor excitement in insanity. 
Given then at bedtime as an hypnotic, the result showed that 
in small doses, under grain l-60th, very little of such action was 
observed, but that a primary period of excitation and restlessness, 
followed by a brief stage of muscular relaxation, prevailed in the 
majority of cases. The continued use of small doses was followed, 
in a week or ten days, by moderate mydriasis, slight suffusion of 
the surface, a sense of dryness in the fauces, slight sudorific action,, 
but not sleep. 
In larger doses, from grain l-60th to grain l-20th, the former 
the initial dose, a group of fourteen cases of insomnia in female 
patients suffering from melancholia acute and agitata, mania acute, 
subacute and chronic and secondary and senile dementia, most of 
whom were hospital inmates of long standing, in whom a tolerance 
of and resistance to medication existed, the amorphous hyos- 
cyamine of Merck was administered 268 times, about an equal 
number of times to each; but one dose in any twenty-four hours,, 
and that usually at bedtime. Careful daily observations w’ere 
made by the writer, assisted by a few intelligent attendants, and 
tabulated. This yielded about nineteen administrations to each 
patient. 
A good night’s sleep, 6 to 7 hours or more, resulted in 73 instances. 
A fair night’s sleep, 4 to 5 “ “ 68 “ 
A poor night’s sleep, 21 to 31 hours, “ 87 “ 
A total failure to sleep, * “ 40 “ 
Total, 268 
Which is 27.23 per cent of success, and about 15 per cent of failure 
of any hypnotic effect. 
Examined in the morning: 
Dryness of the throat and unusual thirst were found in 189 instances. 
Vertigo, “ “ 68 “ 
Muscular relaxation and sense of wretchedness resulted in 148 “ 
Transient mydriasis “ 169 “ 
Pulse quickened and diminished in force “ 199 “ 
Pulse weak or irregular, or intermittent “ 64 “ 
Morning appetite impaired “ 96 “■ 5 
Morning temperature, respiration and condition of skin were not 
affected. The initial doses were hypodermatic, but the drug was 
so promptly active when given by the stomach, with equal energy, 
in the same doses, that the latter mode was preferred, the aqueous 
solution containing a small proportion of alcohol, to insure its 
integrity. The foregoing signs and symptoms do not embrace the 
entire range of physiological effects of the drug, which were best 
demonstrated in another group of cases, in which the sedative and 
motor depressant powers of hyoscyamine were tested during day- 
time. Let it suffice to say of this, that given in full doses, from 
grain l-8th to grain l-10th to active, turbulent cases of mania, acute 
and chronic, and of secondary dementia, within from fifteen to 
twenty minutes, the most complete muscular relaxation followed a 
a brief primary stage of activity, resembling a similar stage of 
alcoholic intoxication. During the secondary, or period of relaxa- 
tion, the following phenomena were prominent, from a state of 
noisy, activity the patient was rather suddenly overcome; 
staggered about, sank down into a seat, sometimes on the floor, in 
complete relaxation, with slowed, often stertorous respiration, 
countenance expressive of misery, widely dilated pupils, marked 
slowing of the pulse, with increased fulness, suffusion of the face, 
hebetude and somnolency, and in about one-fifth of the cases, with 
a slight rise of the axillary temperature. This period would 
continue for from three to four hours, when the patient would 
gradually pass into the third or stage of reaction, during which 
the pulse would be accelerated decreasing in force, until the 
normal balance, and the previous and usual state of the system as 
to the other effects was resumed. 
At this period a sense of dryness of the throat, hoarseness and 
unusual thirst was observed in the majority of cases. In a few 
instances, and not invariably in the same individuals, at the 
height of the relaxation, Cheyne-Stokes respiration occurred, and 
the bladder was emptied involuntarily. In most of these cases 
the appetite was temporarily impaired. The long secondary period 
of relaxation has caused this drug to be used as a means of so- 
called “chemical restraint,” and but few hospital patients can 
acquire sufficient resisting powers to withstand its influence for a 
time at least; but its continued use rapidly breeds a tolerance of 
its sedative and relaxing effects, demanding a frequent increase of 
the dose employed. 
The writer would here explain that it is not the practice of our 
hospital stall' to use chemical restraint, and that our continuous use of 6 
hyoscyamine and similar sedatives ceased after their physiological 
action had been investigated, save in those instances when their 
use was indicated as a special remedial measure. 
As an hypnotic, hyoscyamine, in our hands proved to be 
uncertain and unsatisfactory; very often failing to induce sleep; 
seldom failing to develop a train of unpleasant phenomena such 
as before mentioned. It is in no true sense analgesic. The best 
results from its use in insomnia, were in cases of apparently pure 
motor excitation. It acts least favorably in atonic mental states 
and in mere perturbed nervous conditions; its depressing influence 
upon the circulation being very marked in some such cases. 
Although it has been highly recommended in the passionate out- 
breaks and nocturnal turbulence of the epileptic insane, (Dr. T. 
Brown, British Medical Journal, November 25th, 1882,) and in 
similar states in paretic dementia, (Richter, Neurologisches Central- 
blatt, July, 1882,) yet our experience with females, is against its 
use in these, as well as in all cases of actual brain lesion or acute 
structural metamorphosis. Hyoscyamine is often useful in con- 
trolling the violence of a furious maniac, but its use, in even 
moderate doses, demands caution, as its sedative action on the 
heart is sometimes extreme. A full does causes primarily increased 
frequency of the action of the heart and vascular tonus; 
secondarily, in about twenty minutes, a fall below the normal in 
both, and finally a frequency which is doubtless a reaction toward 
the normal balance of the circulation. It should be used with 
much caution in organic and in marked functional and trophic 
cardiac disorders. The therapeutic value and general scope of 
applicability of hyoscyamine is far below that of its companion 
hyoscine, which we will next consider. 
HYOSCINE—HYOSCINE HYDROBROMATE AND HYDRIODATE. 
This valuable derivative is not chemically of recent origin, 
having been recognized and separated in an impure state by the 
same earlier chemists whose investigations produced hyoscyamine. 
It was originally known as hyoscina, and recognized as distinctly 
differing in physical properties, in physiological action and 
in potency from its brother alkaloid. It is significant that, while 
hyoscyamine is, as before stated, abundantly found in several 
members of the natural order solanacege, hyoscine is only found 
in Hyoscyamus niger, and, in less amount in other henbanes. 
Prior to 1883 no one had succeeded in crystallizing this drug 
save as a double chloride of gold and hyoscine, its closest form 7 
of concentration uncombined was a syrupy fluid, resembling in 
appearance the alkaloid conia, from conium maculatum. As a 
demonstration of the close relationship existing between all the 
active alkaloids of the order Solanacese, it has been recently 
discovered that the supposed special alkaloid of datura stramonium, 
separated from it in 1821 by Brandes and by him named daturine 
is simply a mixture of hyoscyamine and atropia. Another of his 
supposed crystalline vegetable derivatives finally proved to be 
phosphate of magnesium! Again, the effect of oxidizing 
hyoscine by any mineral acid, is the production of tropine and 
tropic acid: Ladenburg took these two oxidation products, united 
them and obtained pure atropia. 
Prof. Edelfsen, after trying many concluded, as did subsequently 
the other manipulators that the most stable and reliable combina- 
tions of hyoscine were the hydriodate, expressed by the formula 
C17, N05 H. I. H2,0, and the hydrobromate, C17, H23, UOfl, H. 
Br, H.2, O, of which the former is only moderately soluble, and 
occurs in small hemihedral prisms of a yellowish white color; but 
the hydrobromate is very soluble in water at all temperatures, and 
in diluted alcohol. It crystallizes in relatively large rhombic, 
sphenoid, hemihedral prisms, colorless and transparent when first 
made but soon changing to white opacity from loss of uncombined 
water. 
Unfortunately hyoscine, on its first appearance in the United 
States was introduced mistakenly as amorphous hyoscyamine with 
which it was confounded, and thus, for a time much confusion 
of ideas had existed among those not very familiar with chemicals, 
which had led to the substitution of hyoscyamine for hyoscine in 
trade orders, and consequently to the most diverse and contrary 
experiences as to its potency and precise mode of action. There 
are various other sources of error which may possibly account for 
the reports of investigators as to the alleged inertness, impotency 
and unreliability of hyoscine, one of which is that it deteriorates 
when long kept or exposed, and thus should be held in stock in 
small amounts, carefully sealed in glass tubes, in a dark and dry 
place. The writer has been reliably informed that there appeared 
in the drug trade of the eastern seaboard at a time of very active, 
early demand and limited supply of Merck’s hyoscine, a fictitious 
substance, under that trade name and label, which crudely 
resembled it, but which was almost inert. 
During the brief run of this fraud, it must have shaped the 
adverse opinion of more than one investigator of hyoscine. Some 8 
of this was forwarded, in its original package, for examination, to 
one of the most experienced importing and manufacturing chem- 
ists in this country, who reported that the package contained no 
hyoscine whatever, and that E. Merck frould certainly disown it. 
Observing proper care, there is no difficulty in obtaining the pure 
drug, which is a uniformly powerful remedy in doses of grains 
l-200th to grains l-50th. Its sedative powers in insanity 
with much motor-excitation were tested by the writer, in the 
same manner as with hyoscyamine, during the daytime, and a 
portion of the cases tabulated. (See the accompanying tables.) 
The results showed that in from moderate grain l-120th, to 
full doses, grain l-90th to l-50th, its physiological action 
on pulse, respiration, temperature, skin and pupils was about 
identical with that of hyoscyamine, but to a much less degree, 
and with much less profound muscular relaxation and sense 
of wretchedness: much less disturbance of appetite than with the 
latter, and very much more hypnotic powei\ In short, the un- 
pleasant effects were mitigated and much sound sleep obtained in 
daytime, by those whose usual state was turbulent. It was 
also found that the range of applicability of hyoscine as 
a sedative extended beyond the cases of more purely motor dis- 
turbance, and that in doses of from grain l-200th to grain 
l-90th it could be relied upon to relieve the mental pain in atonic 
cases, and in those of nervous and so-called hysterical perturbation. 
Its action is far more comfortable, uniform and certain than that 
of hyoscyamine, nor is a tolerance easily established, which would 
demand frequent increase in the dose. Its beneficial sedative 
action in the excitement of paretic dementia and of epileptic 
insanity, is in favorable contrast with the variable and unreliable 
action of hyoscyamine in the same conditions. The writer, after 
much observation of the effects of various preparations of hyos- 
cyamus niger, has met with but one instance, in which its use 
apparently intensified hallucinations of sight or of hearing. 
Our experience with hyoscine proved that both in its sedative 
and its hypnotic action, what effect fails from a full dose, is often 
realized from one or two small doses. As a hypnotic it wTas tested 
in the following tabulated report. (See accompanying tables.) 
A group of twenty cases of insomnia in females suffering from 
melancholia, acute, chronic and agitata; mania, acute, sub-acute 
and chronic ; secondary and paretic dementia and of morphia habit, 
about half of whom were long standing, and tolerant of medicine, 
was given, chiefly at bedtime, in doses ranging from grain l-240th 9 
to grain l-90th, (but as an average grain l-120th,) the pure, crys- 
talline hydrobromate of hyoscine of E. Merck, in aqueous solution, 
348 times. This yielded about seventeen administrations to each 
patient. The effects were closely watched by the writer, assisted 
by a few intelligent attendants and night nurses. Of this number 
A good night’s sleep, six to seven hours or more, resulted in... 246 instances. 
A fair night’s sleep, four and-one-half to five hours, resulted in 55 “ 
A poor night’s sleep, two and one-half to three and one-half 
hours, or broken naps, resulted in 33 “ 
A total failure to sleep resulted in 14 “ 
Total 348 “ 
which yields about seventy-one per cent of success and four per cent of fail- 
ure of any hypnotic effect. 
Examined in the morning : 
Dryness of throat and unusual thirst were experienced in 32 instances. 
Vertigo, slight and transient was experienced in 19 “ 
Muscular relaxation (wretchedness) was experienced in 14 “ 
Transient mydriasis was experienced in. 99 “ 
Pulse quickened and diminished in force resulted in 104 “ 
Pulse weak, irregular or intermittent resulted in 28 “ 
Morning appetite impaired in 29 “ 
Morning temperature and condition of skin unaffected in any case. 
Comparing these gratifying results, which have been fully- 
sustained and corroborated by several years of subsequent daily 
use, with those obtained from the sulphates of hyoscyamine, we 
find a good, reliable hypnotic, with little of the unpleasant action 
of the latter, and a patient will respond to a dose nightly of 
grain l-20th for many weeks, obtaining tranquil sleep, without the 
necessity for an increase in the dose. Dr. E. N. Brush, of our 
staff*, reports much success with it in the insomnia of inebriety and 
the morphia habit. 
It has been, from the time of its introduction, our main reliance 
in certain cases, and it is but just to testify that the condition of 
our disturbed wards has totally changed for the better, in great 
part owing to its judicious administration. An inspection of our 
records and night reports yield abundant testimony to the quieter 
nights and vastly improved sleep of those under our care since 
its use. 
Hyoscine totally fails sometimes, as do all medicines, and it is 
much easier to ask than to answer the pertinent question, under 
what circumstances does it fail, or when is its use contraindicated ? 
The writer has been watching its action daily for several years, 10 
and can only answer that its use is contraindicated in advanced 
cardiac lesion, in grave cardiac weakness, and in states of pro- 
found exhaustion. In mental disorders its range of general 
applicability seems to be almost universal, but with occasional 
failure, for which it is difficult to account. Individual idiosyn- 
crasy is a term used as a shield to our ignorance of its effect on 
certain constitutions, or under certain circumstances. 
The good effects of hyoscine are as evident in atonic, sluggish 
forms of mental disorder, as in the sthenic, and its power to calm 
the violence of paretic and epileptic dementia is only equaled by 
the relief it affords to the insomnia of alcoholism and of the 
morphia habit. It acts promptly, usually within thirty minutes, 
and almost as rapidly, and quite as effectively by the mouth as 
hypodermatically. The smallness of the dose, its tastelessness, 
and the ease with which it may be given in food and in drink, 
further commend it, as does also the improbability of inducing a 
hyoscine habit, as no sense of pleasurable stimulation belongs to 
its physiological action, such as distinguishes that of so many 
remedies, among which is paraldehyde, which we will next 
consider. 
PAKALDEHYDE. 
This is a member of the ether series, is at ordinary temperatures 
fluid, but crystallizes into an ice-like mass at the comparatively 
high temperature of 10° C., and thaws unchanged, and is trans- 
parent, light, colorless: boils at 134°C. (253.7°F.) and has a rather 
unpleasant, ethereal odor, resembling that of aldehyde, and an 
unpleasant burning taste, which renders it difficult to swallow even 
when diluted. Paraldehyde is the condensation product of alde- 
hyde and hydrochloric acid. It is formed by adding to the former 
a small amount of the latter, when the condensation takes place 
with evolution of heat. The product is cooled by ice till it solid- 
ifies, is then pressed to free it from acid, &c., and is finally dis- 
tilled. Distillation with sulphuric acid reconverts it into ordinary 
aldehyde. Aldehyde, its related compound, is as the name implies, 
dehydrogenated alcohol, and is represented by the formula C2, H4, 
O; paraldehyde is simply a modified form of the same, of the 
formula 3 (C2, H4, O), but closely related as they are chemically 
they differ strikingly in their action upon the animal economy. 
Paraldehyde was introduced a few years ago from Germany as 
an hypnotic of peculiar merit, since when its demand has 
steadily increased, notwithstanding the difficulty in exhibiting 11 
even in moderate doses in a palatable form. Its hypnotic dose is 
from two to six grammes, and two grammes of it measures just 
thirty minims—a moderate commencing dose, and twice this a fluid 
drachm, is a fair medium dose—six grammes, or 3 iss a full one. 
It is least unpleasant to take in the following way: B : paralde- 
hyde 3 i; Jamaica rum 3 iv, syrup of acacia 3 iii slightly diluted 
with water; or, Ijf: paraldehyde 3 i, syrup of tolu: 3 iii, cinna- 
mon water 3 iv. 
Of Merck’s paraldehyde one fluid drachm will remain dissolved 
in nine fluid drachms of cold water; but this is almost as difficult 
to swallow as the drug itself. The burning, acrid, choking sensa- 
tion, which is persistent, renders its administration, especially to 
the insane, difficult. In asylum practice it is often convenient, 
but not always desirable, to give it in whisky, which also fairly 
disguises the taste. 
It has been stated that this substance loses its power; changes 
radically, if exposed to the atmosphere for even a brief time. 
This is a fallacy : it is volatile, and loses on exposure, but what 
remains is chemically paraldehyde, to the last drop. Much has 
been written upon this new remedy, based upon scientific research, 
here and abroad. Profs. Arpad Bockai and Barksi of Klausen- 
burg, in a series of observations upon dogs, gave large, but not 
fatal doses of paraldehyde to one group, and similar doses 
of chloral hydrate to another, for long periods. “ The 
organism did not become tolerant of either drug, but its power of 
resistance rather became less, the latter condition being more 
marked with paraldehyde than chloral.” From this they con- 
cluded “ that during long continued use, the dose of these drugs 
need not be increased. The animals perished from the chloral in 
about half the time as from paraldehyde.” This only proves that 
these doses need not be increased when giving these remedies to 
dogs, as in man a tolerance of and resistance to chloral is of com- 
mon experience, and the same may be said, but less frequently, of 
paraldehyde. They finally concluded “ that paraldehyde, given for 
a long time, effects incomparably less injury, than the long con- 
tinued use of chloral hydrate.” A more significant indication of 
its mode of action is revealed in the observations of Drs. Bergesio 
and Mosso (London Medical Record, Oct. 15, 1884), who “having 
a patient who had lost a large portion of the calvarium, they were 
enabled to make a study of the cerebral circulation, which con- 
firmed the view that the brain is anaemic during sleep. Paralde- 
hyde gave the same result as natural sleep. Morphia and alcohol 12 
notably increased endo-cranial congestion : that the hypnotic effect 
of these two latter drugs does not depend on change in the blood 
pressure, but upon some special action, possibly of a chemical 
nature, upon the cerebral cortex.” We can confirm the statement 
that paraldehyde does slowly diminish the force and frequency of 
the heart’s action. 
Dr. Clouston says (in American Journal of Medical Science, 
April, 1889), “this pure hypnotic,after extensively employing it, I 
like better than any I have tried. * * * * does n0(; inter- 
fere with the appetite, nor does it disturb the stomach or bowels. 
After a paraldehyde sleep there is no lassitude; no headache.” 
Dr. G. F. Duffy concludes from a long continued series of experi- 
ments that “ it acts first on the cerebral hemispheres and causes 
torpor without preliminary excitement. After the hemispheres the 
action extends to the medulla, then to the cord. A lethal dose 
suspends the function of the medulla and the respiratory centre, 
and the action of the heart ceases after the respiration.” 
It seems to be an established fact that in common with urethane, 
this drug is antagonistic to the action of strychnia, even in poison- 
ous doses. For several years past the writer has steadily used and 
carefully studied the effects of paraldehyde in our hospital, and has 
been encouraged to continue on account of its purely hypnotic 
action in the insomnia of certain forms of insanity, in the average 
dose of one fluid drachm; disguised with syrup tolu, and one of 
the aromatic waters. This has proved the most suitable method 
as, when alcohol, in any form, or spirits chloroform or other active 
substance is used as an excipient, as has been often recommended, 
we introduce an unknown quantity into the problem of its effect 
upon the organism, and then who is to say whether drug or 
excipient induced the repose, or to what extent its action was mod- 
ified thereby ? In our hands it has acted best in cases of melan- 
cholia in its various forms; in cases with a strong hysterical 
element; in those beset with delusions of fear, of doubt, or of 
dread of impending calamity; in the agitated who pace the floor 
at night, wringing their hands, and in the demented who are 
ordinarily quiet in daytime but are disturbed at night. Much less 
success has attended its use in mania of all forms, either in mod- 
erate doses repeated at short intervals, or in a single full dose at 
bedtime; the latter answering better than the former, as, in excited 
states there is a primary excitation often produced which is 
repeated and intensified by subsequent doses. In the conditions 
previously cited in which the drug acted most favorably, this 13 
primary excitation was seldom observed ; the patient sinking to 
sleep usually within thirty minutes after its ingestion, obtaining 
from five to seven hours of tranquil repose, and awaking re- 
freshed, without unpleasant after-effects. This in the majority of 
such cases, but not always so; for in twenty cases there were two 
(of melancholia agitata) in whom the respiration was weakened 
and hurried, with a sense of cardiac oppression, after any dose. 
In several other instances, in different cases, after an evening dose 
of f 3 i, followed by sleep, were experienced headache (frontal) nau- 
sea, coated tongue, and increased mental depression, which yielded 
upon the withdrawal of the medicine, and returned upon its sub- 
sequent use. It sometimes caused similar sensations in instances 
when sleep failed to follow its use at bedtime. In about half of 
the cases observed, which was twenty-six in all, was the amount of 
urine apparently moderately increased by its continued use, the 
urine being paler and more watery, but quite free from ethereal 
odor. Its elimination takes place mainly through the lungs, but, 
in part also, evidently by the skin; the sweat and the expired 
breath of those taking it nightly, being seldom free from the char- 
acteristic odor. When pain is an element in insomnia paraldehyde 
fails to overcome it. We have observed, in a few cases of epilep- 
tic insanity, in whom the paroxysms were chiefly nocturnal, 
much improved sleep, and marked diminution in the number and 
severity of the paroxysms, by a bedtime dose of one fluid drachm. 
Paraldehyde was tested by the writer in a group of twenty-six 
insomnious hospital cases as follows: The drug was given 424 times, 
about an equal numer of times to each. There were of mania, 
acute 3, subacute.3, chronic 4, melancholia acute 2, agitata 2, sub- 
acute 3, chronic 3, dementia senile 1, secondary 3 and epileptic 2 
cases—26 in all. 
The doses ranged from 3 i to 3 ii; but the former in the major- 
ity of cases, and but one dose was given to each patient at bed- 
time; all other drugs being withheld. 
Complete success, from six to eight hours or more of con- 
tinuous sleep, resulted in 291 instances. 
Pair success, from four-and-one-half to five hours or more 
of continuous sleep, resulted in. 22 instances. 
Partial failure, from three to four hours or broken naps, 
resulted in 42 instances. 
Total failure to sleep resulted in 69 instances. 
This yields of complete success about 68.7 per cent, and 
of total failure of hypnotic power .... 16J per cent. 14 
Paraldehyde is a fairly reliable hypnotic, chiefly in the asthenic 
forms of mental disorder, and, but for its unpleasant taste and 
lingering effect upon the expired breath, could be used in the 
asylum practice much more freely than it now is. No case of death 
from its legitimate use has, as yet been reported, although it has 
been and may safely be used in the insomnia of cardiac affections, 
with less risk than any other allied compound save sulphonal. A 
few cases have been reported in which the paraldehyde habit has 
been contracted ; but using due professional caution, the danger 
of so doing would be trifling. 
The sleep produced by this drug has often been compared to that 
by chloral hydrate; but the consensus of opinion among those 
who have investigated both substances is that paraldehyde is the 
much safer of the two to employ continuously, as in nervous 
insomnia and in that of drunkards it is much superior to chloral; 
less irritating to and better born by the stomach; it is 
not a cardiac depressant, nor does there usually exist the necessity 
for rapidly augmenting the dose, as is so frequently the case in the 
steady use of chloral hydrate. 
URETHANE. 
This is another member of the ethereal group of hypnotics, and 
is chemically the carbamidate of ethyl, of the formula (NH2, C04, 
C2 H6). It is a solid, in large, irregular plates and crystals, opaque 
white in color, without odor, and of a taste at first slightly sweet, 
afterward faintly bitter: is readily soluble in water at all temper- 
atures, forming a permanent solution. This recent addition to the 
hypnotics comes to us from Germany. Its advent was, as usual, 
heralded by such glowing accounts of its powers, as might have 
aroused the hope that the ideal hypnotic was upon us; but calm 
experience has failed to verify its superiority over paraldehyde. 
Merck’s pure urethane is the one principally, if not universally 
used in this country, and appears to be pure and uniform in its 
action and physical properties. From experiments by Prof. Coze 
with it in the lower animals, it would appear that, in a large dog, 
the effect of strichnia grain l-5th was thoroughly counteracted by 
grains 75 of urethane, and that the animal survived both doses; it 
further appeared that the amount of oxygen in the blood is 
notably increased by its presence, which may possibly account for 
the frequent failure of urethane to produce sleep. Unlike paral- 
dehyde and sulphonal, it appears to be moderately analgesic, and 
some relief has resulted from its use in the restlessness from pain 15 
in gout and in rheumatism. The Italian asylum physicians, after a 
very thorough trial, report a rather unfavorable experience with it. 
Dr. Sighicelli, of the Ferrara hospital, says: “Urethan proved 
uncertain in all forms of insanity, as an hypnotic, even in melan- 
cholia and dementia. Respiration was shallower and slower: 
on the other hand the heart acted more powerfully and quickly.” 
Drs. Otto and Koenig (Centralblatt fur JVerven Ileilkunde), after 
extensive trial among the insane, also report generally unfavorably 
upon it; but as having most hypnotic effect in cases of paralysis 
and of dementia without excitement, but with restlessness and 
nocturnal vigilance; but then in doses of from 5 to 12 grammes, 
or 75 to 180 grains, which is much in excess of the average dose. 
Krapelin and Rothenbiller had fair success with it in similar quiet 
cases, but ill success in disturbed conditions; the former observer 
having never seen any unpleasant after effects, 60 per cent of his 
paralytic dements obtaining from six to eight hours of continuous 
sleep, within fifteen minutes after having taken from 1 to 3 
grammes of urethan. 
Dr. II. Williams, {Jour. Amer. Med. Assoc. Jan. 22, 1887,) of 
the medical staff of the Arkansas State Asylum, reports a most 
favorable hypnotic effect from urethane in cases of mania, with 
much excitement, in the moderate dose of grains 15. He says: 
“I have found sound, natural sleep to result uniformly after this 
dose.” In our hospital practice we have not been so fortunate, 
after a fair trial of it, in various doses, and in the various phases 
of mental disorder. Given in the published dose of 15 grains, it 
had but little hypnotic effect in cases of mania in any stage, or in 
any disturbed conditions, while in doses of from 30 to 35 grains 
there was little more sleep, with considerable morning discomfort, 
of which the chief elements were nausea, loss of appetite, and 
persistent frontal headache. In about one-fifth of the cases of a 
quieter character, such as melancholia, dementia, &c., the drug 
acted fairly as an hypnotic, but very irregularly, in doses of from 
15 to 20 grains. More than these amounts frequently produced 
impairment of appetite and headache. A full night’s sleep, from 
seven to eight hours, having been rather exceptional, in any con- 
dition, under its influence. Repeated subsequent trials with 
different lots of the drug, have not proved any more satisfactory 
in our hands, and when, therefore, very recently, a new solid 
ethereal substance was announced by the chemists of Germany, as 
the coming hypnotic, we were prepared to look upon it askance. 
This compound, sulphonal, deserves, however, more than a 
passing notice. 16 
In the treatment of insomnia from whatever cause demanding 
medicine, we aim to use a remedy of which sleep is the sole, or at 
least the predominant physiological action. It was originally 
claimed by the manufacturers of sulphonal in Germany, that its 
sole effect was to cause sleep of a quality very similar to that of 
nature, and of the many investigators of it, both here and abroad, 
there has not been one to report unfavorably of its action. The 
very general consensus of opinion in its favor is all the more 
singular from the fact that of all the others discussed here 
different examiners have had the most diverse and puzzling 
experiences in their use. The almost universal report of sulphonal 
is that it has little or no effect upon the vast majority of insomnious 
subjects, save the important one of increasing, prolonging the 
natural tendency to sleep; that its action is not narcotic, but purely 
hypnotic; that the pulse, pupils, temperature, respiration, appetite 
and the secretions remain practically unaffected after its daily use 
for indefinite periods, and that it is finally promptly eliminated 
from the system, principally by the kidneys, without irritation or 
detriment to those organs. Sulphonal is also a member of the 
ether series, and is a crystalline, white, solid, with a slight ten- 
dency to effloresce when exposed to the air, and is easily powdered, 
emitting, when warmly triturated, a faint odor of sulphur, and it 
is almost tasteless. It is singularly insoluble in any of the potable 
solvents, as water, dilute acids or alkalies, or very dilute alcoholic 
solutions. It is soluble in two parts of ethylic alcohol (95 per ct.) 
and one of ether, but this is not potable, and any dilution of this 
with water precipitates the sulphonal. It may be given in pow- 
der, or a dose of the finely powdered drug may be suspended in 
three or four fluid drachms of cold water by means of gum acacise 
and syrup, which should be thoroughly shaken before using, and 
but one dose prepared at a time, as it rapidly settles to the bottom 
of the container. It may be conveniently given also, in hot gruel, 
or in milk. 
The name sulphonal is evolved from the compound word which 
expresses its chemical identity—diaethyl-sulphon-dimethyl-methan, 
and the actual solubility is one part of the drug to about 100 parts 
of cold, and one to about 18 or 20 of boiling water, which, of 
course, drops it on cooling. It is unaffected by acids, alkalies or 
oxidizing agents: a very stable compound, of the symbol 
(CH3)2 C(Cj,H5,S02).3, and was discovered and named by Prof. 
Baumann, who, with Prof. Kast, of Freiburg, tested, first on dogs, 
SULPHONAL. 17 
afterward on normal human beings, finally upon iusomnious per- 
sons insane and otherwise ill, its physiological effect in a series of 
clinical observations, which showed that in doses of 2 to 3 gram- 
mes (grains 30 to 45) to persons in health, it produced lassitude, 
hebetude and sleep; in the same doses to those suffering from 
nervous and febrile insomnia it caused a sound, refreshing sleep 
of from five to six hours’ duration, within from one-half to two 
hours after administration. Subsequently Prof. Cramer and 
Doctor Rabbas obtained similar results upon insane patients in the 
Marburger Irrenheilanstalt. In no instance did it effect unpleas- 
antly or dangerously; produced no evil effect afterward upon the 
circulation, respiration, appetite, digestion, secretions nor excre- 
tions. The pupils remained unaffected. “ Although somewhat 
slower in taking effect than chloral hydrate (Notes on New Reme- 
dies for June, 1888) the action of sulphonal is more prolonged. 
Doses of 2 to 3 grammes proved safer and more effective than 
proportionally larger doses of amylen hydrate. Another peculiar 
and valuable attribute of sulphonal is that its prolonged use does 
not weaken its physiological effect, nor does it produce the desire for 
a narcotic, that makes the use of chloral (and some other drugs) 
so dangerous. Additional and general investigation will doubtless 
verify the above observations and insure the popularity of this 
new hypnotic.” 
The papers by Prof. Ivast and Dr. Rabbas were published in 
1888 (in the Berliner Klin. Wochen., Nos. 16 and 17.) The latter 
considers it more desirable than paraldehyde or amylene, and as 
compared with chloral hydrate, sulphonal is less prompt but more 
lasting in hypnotic effect. Further corroborative evidence will be 
found in papers by Langgard u Rabow, (Ther. Monatshefte, for 
May, 1888); by Salgo, ( Wiener Med. Wochen, No. 20); by Rosin, 
(in Berlin. Klin. Wochen, No. 18); by Astreicher, (in the same); 
by Cramer, (MiXnch. Med. Wochen, June 12, 1888, p. 395 ); by 
Schwalbe, (Deutsch. Med. Wochen, June 21, 1888, p. 499); and by 
Rosenbach, (Berlin. Klin. Wochen, June 11, 1888, p. 481.) 
Astreicher found it best to give the dose several hours before bed- 
time, as it was rather slower to act than some others of the same 
class; but he found it none the less reliable, especially in the 
insomnious insane. Cramer’s cases were all of the latter class, and 
in his 407 trials on 92 insane subjects he had positive success “ in 
92.6 per cent, i. e. from five to nine hours of unbroken sleep, 
resulting in about half an hour after its administration. He had 
not an instance of unpleasant effect, “ though in one case grains 18 
480 in six days, and in two others grains 45 daily were given for 
two months.” Schwalbe’s results are of especial value and 
reliability, as they were exhaustive and carefully tabulated. He 
selected fifty patients ill of various bodily and of mental diseases 
and disorders, all insomnious, and got “ a prompt and satisfactory 
hypnotic effect in 66 per cent.” But what is of especial value is 
the fact that “ of twenty-four cases of purely nervous insomnia, 
success was complete in 90.3 per cent. 
To such cases it seems best adapted, for in instances where the 
sleeplessness was the direct result of pain, or of decided irritation, 
but 44.4 per cent slept at all, and these but for a few hours. 
Schwalbe agrees with Kast that the drug is purely hypnotic, not 
narcotic. It seems decidedly most valuable in perturbed nervous 
and unbalanced cerebral cases, but in no sense is it analgesic, nor 
does it allay the nocturnal cough of phthisis, or bronchitis. 
Contrary to the experience of Kast, Schwalbe found that it did 
not relieve cardiac dyspnoea. 
In but 12 per cent of all cases so far investigated in Europe, 
were there any ill-effects from its daily use, and this was confined 
to slight headache or to transient vertigo. 
Schwalbe’s experience of it in children was satisfactory in doses 
of four grains: in male adults in doses of from grains 15 to 30, 
and in female in less doses from grains 12 to 25. 
In the department for females of the Pennsylvania Hospital for 
the Insane, the writer has observed carefully the action of 
sulphonal upon a group of twenty cases of mental disorder, all of 
whom had been quite insomnious, so as to resist the sedative force 
of the bromides with ergot, urethane, tinct. hyoscyamus, English. 
Eight of them resisted all these and also paraldehyde, seven of 
them resisted all these as well as opium and chloral hydrate in the 
usual doses, while all but one of them were usually controlled, i. e. 
slept, by the use of hyoscine hydrobromate, in doses ranging from 
grain l-120th to l-90th. The group comprised three cases of acute 
melancholia with delusions of fear of bodily harm and of impend- 
ing calamity; one of dementia, senile; one of melancholia agitata; 
two of epileptic insanity; two of melancholia, chronic; three of 
mania acute; two of mania sub-acute; one of mania chronic; 
four of secondary dementia; and one case of nervous disorder with 
threatened insanity. Of these all the subacute and the chronic 
were much accustomed to the elfects of sedatives, hypnotics, &c., 
all requiring night medicine regularly. But one moderate dose of 
sulphonal, suspended by acaciae and syrup in water, was given each 19 
patient about an hour before bedtime, and in no instance was the 
dose repeated, nor were any of them taking any other drug. The 
group was intelligently observed at night by nurses sitting up. 
The results were carefully observed and tabulated. The drug was 
given 480 times, no patient receiving in all less than twenty-one 
doses. In thirteen of the cases the nightly dose was 15 grains; 
in four it was 20 grains; in one it was 21 grains; and in one case 
it was 22 grains. 
The results were as follows: 
An excellent effect, i. e. 6£ to 9 hours of continuous sleep, in 381 instances. 
A fairly good “ 4 to 5 “ “ 34 “ 
An imperfect “ 2 to 3 “ (or broken naps) 42 “ 
No hypnotic effect 23 “ 
Total, 480 
This yields of positive successes 79.2 per cent of the entire number, and of 
total failure of hypnotic action 4f per cent. 
It is gratifying to note the general improvement which attends 
the regular nightly sleep produced by such a singularly harmless 
drug as sulphonal appears to be. In but seven instances had its 
use for many continuous nights been followed by unpleasant 
effects, and these were limited to transient morning headache and 
slight vertigo in two of the patients taking the larger doses. As 
a rule, with very few exceptions, the patient rises with the usual 
appetite; free from a sense of malaise. In no instance did it 
produce any appreciable effect upon the temperature, pulse, 
respiration, skin, kidneys nor pupils, nor did the digestion appear 
to be at all impaired by its regular use. The sole physiological 
action appeared to be the production of sleep, usually quite restful 
and prolonged. 
As the results were good in these hospital cases, tolerant of such 
drugs, would not probably less doses overcome the insomnia of 
the simply weary, over-worked or irritable nervous system ? It 
should prove useful in the insomnia of general disease of which 
pain is not a prominent factor. It will not ease pain, nor will it 
bring sleep when pain is present as a continuous sensation, but it 
will allay nervous restlessness, vigilance and agitation. In cases 
of acute mania, with much motor activity, it does not act nearly 
so promptly nor effectually as hyoscine, in any doses. Male adults 
usually require a larger dose by from three to five grains than do' 
females. In the latter a fair average dose is from 15 to 18 grains, 
but there need be no fear in increasing the amount to 30 or 35 20 
grains. Should no hypnotic effect follow the latter quantity the 
remedy will fail in any amount. 
RECAPITULATION OF RESULTS—HYPNOTIC ACTION. 
Hyoscine—positive success, about 71 per cent. 
“ —total failure, 4 “ 
Sulphonal—positive success, 79.2 “ 
“ —total failure, 4§ “ 
Paraldehyde—positive success, 68.7 “ 
“ —total failure, 16f “ 
Hyoscyamine—positive success, 27.23 “ 
“ —total failure, about 15 “ 
Urethane—positive success about 13 “ 
“ —total failures, numerous. 
Iii concluding this paper the writer would pass by with a brief 
notice such more or less hypnotic substances of more recent intro- 
duction, or of revival, as hypnone, amylen-hvdrate, amylen-phenate, 
ethyl-bromide, ormosine (from the ormosia dasycarpa) Jamaica 
dogwood, spartein, kava-kava, methylal, because, with scarcely 
an exception, they have failed to stand the test of applicability to 
the treatment of insomnia in the insane. Those of the ether series, 
as hypnone, ethyl-bromide and the amylen compounds are either 
violent, variable and uncertain in their action and are undesirable 
from their unpleasant taste, or they disagree with the stomach, 
impair digestion, and cause unfavorable secondary disturbances. 
Methylal is said by Krafft-Ebing to be the best remedy that he 
has tried for pai’oxysms of delirium tremens. The various amyls 
and methyls have received, from time to time, favorable notice 
from contributors to current medical literature, but the mere fact 
of their remaining in the background of our therapeutical array, 
is significant of the retirement to which they will be relegated in 
the near future. The present paper seems to the writer, after 
much careful trial, and long-continued study of effects, to embrace 
the most reliable, least variable and least harmful of the more 
recently introduced hypnotics applicable to the treatment of some 
forms of insomnia in the insane. If it will be found that in doing 
so any light has been shed upon the subject of the action of these 
modern hypnotics, he shall feel fully recompensed for the contin- 
uous efforts put forth for several years, and proceed encouraged 
toward further investigation.* 
♦Read at the annual meeting of the Association of Medical Superintendents of 
American Institutions for the Insane, held at Newport, R. I., June 18-30, 1889.