Curarine, when pure, forms colourless, four-sided, very hygroscopic prisms of bitter taste, and weakly alkaline reaction; soluble in water and alcohol in all proportions, but with difficulty soluble in amyl alcohol and chloroform, and not at all in anhydrous ether, bisulphide of carbon, or benzene. The base forms crystallisable salts with hydrochloric, nitric, and acetic acids. Curarine strikes a purple colour with strong nitric acid. Concentrated solutions of curarine mixed with dilute glycerin, give an amorphous precipitate with potassic bichromate, and the precipitate treated with sulphuric acid strikes a beautiful blue colour. Curarine chromate is distinguished from strychnine chromate by its amorphous character, and by its comparatively easy solubility. If the chromates of strychnine and curarine be mixed, and the mixed chromates be treated with ammonia, strychnine will be precipitated, and curarine pass into solution, thus forming a ready method of separating them.
§ 505. Physiological Effects.—According to Voisin and Liouville’s experiments, subcutaneous injections of curare on man cause, in small doses, strong irritation at the place of application, swelling, and pain. The temperature of the body is raised from 1° to 2°, and the number of respirations increased from 4 to 8 per minute. The pulse becomes somewhat stronger and more powerful. The urine is increased, and contains sugar. Large doses administered to warm-blooded animals cause, after a short time, complete paralysis of voluntary motion and of reflex excitability, and the animal dies in asphyxia, the heart continuing to beat.
This state is best produced for the purpose of experiment on frogs, and, indeed, is the best test for the poison. A very minute dose injected beneath the skin of a frog soon paralyses both the voluntary and respiratory muscles; the animal continues to breathe by the skin; the heart beats normally, or, perhaps, a little weakly, and the frog may remain in this motionless condition for days and yet recover. Only curare and its congeners have this effect. By tying the femoral artery of one of the frog’s legs before administering the poison, an insight into the true action of the drug is obtained. It is then found that the reflex excitability and power of motion in the leg are retained, although all the rest of the body is paralysed. The only explanation of this is that curare does not act centrally, but paralyses the intramuscular ends of the motor nerves. Curare is eliminated partly through the liver and partly through the kidneys. Dragendorff found it in the fæces, while a striking proof that it is excreted by the kidneys is given by the experiment of Bidder,[546] in which the urine of a frog poisoned by curare was made to poison a second, and the urine of the second, a third. The easy excretion of curare through the kidneys furnishes an explanation of the relatively large dose of curare which can be taken by the stomach without injury. A dose which, given by subcutaneous injection, would produce violent symptoms, perhaps death, may yet be swallowed, and no ill effects follow. It is hence presumed that, in the first case, the poison is, comparatively speaking, slowly absorbed, and almost as fast separated, and put, as it were, outside the body by going into the urine; while, in the other case, the whole dose is thrown suddenly into the circulation.
[546] Arch. f. Anat. u. Physiol., 1879, p. 598.
§ 506. Separation of Curarine.—It is hardly probable that the toxicologist will have to look for curarine, unless it has entered the body by means of a wound or by subcutaneous injection; so that in all cases the absorbed poison alone must be sought for. The seat of entry, the liver, the kidneys, and the urine are the only parts likely to be of any use. Dragendorff recommends the extraction of the tissues with water feebly acidulated with a mineral acid, to precipitate albuminous matters, &c., by strong alcohol, and separate, by means of benzene, fatty matters. The liquid is then made alkaline, and shaken up with petroleum ether, which removes certain alkaloidal matters. It is now evaporated to dryness, mixed with finely-powdered glass, and extracted with absolute alcohol. The alcohol is evaporated to dryness, and any curarine extracted from this residue with water. By very careful drying up of this last extract, and taking it up in alcohol, the alkaloid is said to be obtained so pure as to respond to chemical tests. The identification may be by the colour reaction of sulphuric acid described ante, in all cases supplemented by its physiological action on frogs.[547]
[547] It is known that curare may cause slight symptoms of excitation before the paralysis comes on. M. Couty has succeeded in isolating these symptoms by employing feeble extracts of Strychnos triplinervia, or small doses of certain native preparations. By these means, in dogs, a new phase of intoxication may be present for ten or even twenty minutes. In the first instance the animal is agitated, jumping, scratching, barking, as if in a state of general hyperæsthesia. Then it presents half choreic shocks or tremors; the pupils dilate, and are alternately dilated and contracted. The heart’s action is increased or diminished in frequency; sometimes there is vomiting, micturition, or defecation; and there is always salivation. Finally, the central and peripheral temperature are raised, and the excitability of the muscles and nerves becomes highly increased. With the native preparation of curare, it is impossible to prolong this stage, and symptoms of paralysis soon become associated with those of excitement. The choreic shocks were found to be arrested by section of the sciatic nerve. Other experiments proved that the spasms originated from the spinal cord, and were influenced by its preceding functional condition. If the cord was tied in the mid-dorsal region, and the curare injected, the spasms were still produced in the hind legs; but if, after the operation, the excitability of the posterior segment became lowered, the spasm was no longer produced in the hind legs. This dependence on a perfect functional activity is a point of difference of these spasms from those produced by strychnine, and by asphyxia. The action of small doses of curare is not, however, limited to the spinal cord. The diminished frequency of the heart continues after section of the pneumogastrics, and will even occur if the pneumogastrics have been previously divided. From these facts M. Couty considers that curare must not be regarded as entirely destitute of a “convulsant” action, nor of an action on the central nervous system.