MATERIA MEDICA AND THERAPEUTICS.
Experimental Researches on the action of Quinine, especially in large
doses. A Memoir submitted to the Jlcademy of Science. By M. Brec-
quet. Report of MM. Andral, Rayer, and Lallemand.—M. Brecquet
records the effects on the principal organs of the animal economy, of
sulphate of quinine, in doses of fifteen grains and upwards. His ex-
periments have been made upon living animals; to these he adds
observations on patients to whom he has administered the remedy in
the above-named doses.
1.	Effects on the organs of circulation.—These were of two kinds,—
first, as regards the frequency; secondly, as regarded the force of the
pulsations of the heart. The frequency of the pulse was variously
reduced from eight to forty beats in the minute.
Alterations in the force of the heart’s action were observed by the aid
of M. Poisseuille’s haemadynamometer applied to the carotid artery of
animals, in whom at the same time solution of sulphate of quinine was
injected into the left jugular vein. Varying with the quantity injected,
the force was observed to be diminished from a seventh to a tenth, a
fourth, a third, and a half; and at last, on injecting thirty grains of the
bisulphate in about four ounces of water, all pressure disappeared, the
heart’s action ceased, and instant death by syncope ensued. These
effects were observed to follow regularly, whether the quinine were
administered by injection into the vessels, by the stomach, or by inser-
tion into the cellular tissue.
2.	On the nervous centres.—Injected directly towards the brain by
the carotids or ascending aorta, great cerebral excitement and convul-
sions were produced. If the quinine reached the brain by the more
indirect route of the general circulation, agitation, headache, vertigo,
tinnitus aurium, paralysis of the nerves of the special senses, muscular
twitching and subsultus tendinum, apparent intoxication, then general
collapse and loss of all voluntary power. Dissection generally disclosed
great congestion of the brain and its membranes, and even meningitis.
3.	On the organs of respiration.—No appreciable effect was observed,
except what might be referable to the slower propulsion of the blood by
the heart.
4.	On the digestive organs.—Inflammation of the mucous membrane,
attended with its usual symptoms, though not generally of a severe
character.
5.	On the urinary apparatus.—Pain, frequent micturition, hsematuria,
dysuria, and retention, have been noticed, but always in a slight degree.
6.	On the organs of generation.—Uterine haemorrhage of the female,
and debility of the organs in the male.
7.	On the skin and the subcutaneous cellular tissue.—Numbness and
coldness of the surface, ecchymosis and petechise, more or less exten-
sive.
8.	On the blood and other animal fluids.—When blood drawn from
the vessels was placed in contact with solution of quinine, it became
liquefied, and the globules were destroyed ; but in order that such effects
should take place in the living body, the presence of a much greater
quantity than can be taken by the stomach would be required. Animals
poisoned by this medicine did not present this liquid state of the blood,
but an increase in the proportion of fibrin was found. No trace of
quinine could be discovered in the milk or mucous secretions.
The absorption and elimination of quinine in reference to its thera-
peutical employment, was ascertained by noting the period at which a
precipitate appeared in the urine, on the addition of the bi-iodide of
potassium, and by observation of the symptoms referable to the nervous
system. Thus it was observed that the sulphate in doses exceeding
three grains is absorbed in from half an hour to two hours, and pro-
duces its physiological effects in another hour. These will continue for
about half an hour. A dose of fifteen grains in six hours continues to
manifest its influence for from five to six hours. Thirty grains admin-
istered in two hours, produce symptoms lasting from twelve to fifteen
hours. When the sulphate has been administered for several days, the
effects continue many days after it has been withdrawn. The medi-
cine is completely eliminated at the end of ten or twelve hours after
small doses, and in about forty-eight or seventy-two hours after large
doses.
Women and children are more susceptible of its influence than men ;
and the stature and strength of the individual modifies its effects. Loss
of blood increases also its influence, diminishing its stimulating, and
increasing its depressing action. Opiates act in a similar manner, while
alcoholic stimulants have a reverse operation.
In reference to its therapeutic properties, M. Brecquet found that the
sulphate is the most active of all preparations of quinine ; that the alka-
loid itself has an action identical with the sulphate, as has also cincho-
nine, but that the latter is by one-third less powerful; that quinoidine
has the same action as quinine on the nervous system, but is much
more irritating to the alimentary canal.
M. Brecquet found the solution of sulphate more active by one-half
than the same compound in the dry state. Administered by enemata,
absorption was found to take place more rapidly than when it was given
by the mouth, but the effects lasted a shorter time, and the alkaloid
scarcely produced its physiological action. Employed for frictions,
ointments, lotions, and other endermic methods, the absorption was
very feeble, and no physiological action whatever could be traced.
The physiological and therapeutical effects of this medicine were
more regularly and powerfully obtained by its administration in repeated
doses; its exhibition therefore requires to be continued for a certain
period.—Lond. Med. Gaz., from Comptes Rendus.