FORMULA: C34H47NO11 (Freund and Beck). MOLECULAR WEIGHT: 643.55.
SYNONYMS: Aconitia, Aconitinum.
Preparation, History, and Chemical Composition.—Wright's process is as follows: Exhaust powdered aconite root with alcohol, in which has been dissolved 0.5 per cent of tartaric acid. Distill the alcohol to complete evaporation at a low heat or in vacuo. Dilute the extract so obtained with a like quantity of water, remove the oil and resin by filtration, add ether or petroleum naphtha to remove the remaining resin, and precipitate with excess of salt of tartar. Dissolve the precipitate in ether, mix again with petroleum naphtha and evaporate. This process will yield a crystalline aconitine, having, however, a small amount of adherent amorphous product, not wholly separated by the potassium carbonate. Other methods, in which sulphuric acid and ammonia water are chiefly employed, yield an amorphous product. The chemistry of aconite and aconitine has been the subject of much controversy. That the mineral acids produce the amorphous form, and that tartaric acid does not decompose aconitine, were first shown by Duquesnel, in 1872. Groves first obtained it in crystalline form. Wright (1875-1880) showed that aconitine could be resolved by heat or by saponification with an alkali into benzoic acid and aconine (C26H39NO11), an amorphous body, identical with acolyctine and napelline, and having a bitter, non-acrid taste. Aconine dissolves freely in water, alcohol, and chloroform, but is nearly insoluble in ether. Wright assigned to aconitine the formula C33H43NO12, and found its fusing point to be 183° C. (361.4° F.). Subsequently Dunstan and Ince, in 1891, gave it the formula C33H45NO12; fusing point 186.5° C. (367.7° F.). In 1894 and 1895, Freund and Beck pronounced aconitine to be an acetyl-benzoyl derivative of aconine, establishing for the latter alkaloid the formula C25H41NO9; hence, for the pure aconitine C34H47NO11, having a fusing point at 197-198° C. (386.6-388.4° F.). The results obtained by Dr. Freund seem now to be generally adopted as correct. Commercial aconitine has repeatedly been shown to be of various degrees of strength, and is a mixture of the foregoing alkaloids, together with pseudaconitine (C36H49NO12) and picraconitine (C31H45NO10), the former being capable of conversion into dimethyl-protocatechuic acid (veratric acid) (C9H10NO4) and pseudaconine (C27H41NO9). [For a recent investigation in this direction, see Dohme, Proc. Am. Ph. A., 1895, p. 206].
Description.—The pure alkaloid has a slightly bitter, but acrid, taste, and dissolves easily in alcohol, ether, chloroform, and benzol. That made according to the British Pharmacopoeia, is a white, amorphous body, sparingly soluble in cold, more readily in hot water, and still more freely in ether and alcohol, but it is almost insoluble in benzin. It produces protracted numbness, preceded by tingling, when rubbed on the hands or skin. Pseudaconitine alone is often sold for crystalline aconitine. According to Dr. E. R. Squibb (Ephemeris I., 135), no aconitine should be accepted of which 1/800 grain dissolved in 1 fluid drachm of water, and held in the anterior portion of the mouth (first well rinsed) for 1 minute, which will not, within 15 minutes, produce a pronounced aconite sensation short of, but bordering on, numbness. Most of the commercial aconitine is now made by patented processes.
Action, Medical Uses, and Dosage.—The effects of this drug are those mentioned under aconite, though greatly intensified, as it is a much more powerful agent than the parent drug. The ointment or alcoholic solution, applied to the unbroken skin, produces tingling, prickling, and anaesthesia. Neither redness nor heat are observed, however, from such use. Upon broken skin, intense burning is felt, and when placed upon the ocular membranes violent irritation is produced. It should never be used as an internal agent, its effects being such that its employment, when the drug is pure, is too hazardous. Owing to the variability of the commercial product the dosage can not safely be regulated.
Dr. Turnbull introduced aconitine as an external agent in neuralgia and rheumatism, in the form of tincture or ointment. His ointment is composed of aconitine, 16 grains; olive oil, half a drachm; lard, an ounce. Mix. To be rubbed for several minutes over the affected part. The tincture is made by dissolving 8 grains of aconitine in 2 fluid ounces of alcohol. In using these preparations they should not be applied where the skin is broken or excoriated. Even as an external agent its use should be discouraged. When employed internally, as it has been by some physicians, the dose ranges from 1/500 to 1/96 grain; as a beginning dose not more than 1/250 grain should be administered. We have known alarming symptoms to be produced by 1/500 grain of aconitine.