Physostigmatis Salicylas, Physostigmine Salicylate.
Physostigmine salicylate, C6H4(OH)COOHC15H21N3O2, a salt of the alkaloid physostigmine, may be prepared by neutralising a solution of 10 of physostigmine in warm ether with a solution of 10 of salicylic acid in ether until a drop of the liquid on moistened blue litmus paper produces a faint reddening. After the crystals have separated, they are collected, and dried at a very gentle heat. Physostigmine salicylate is official in the U.S.P. It occurs in the form of colourless or slightly yellow, glistening needles, or short, columnar, odourless crystals, having a faintly bitter taste. Solutions should only be tasted cautiously. The diluted aqueous solution is neutral; the concentrated alcoholic solution reddens blue litmus paper slightly. The aqueous solution becomes pink on standing for some time, owing to formation of rubreserine. Physostigmine salicylate softens on heating, and becomes slightly yellow at 160°, melting at 179°. On ignition it leaves no residue. The aqueous solution gives with ferric chloride a deep violet colouration (due to the salicylic acid); with calcium hypochlorite a red colouration; with a drop of caustic alkali solution a cherry-red, changing to darker red, and, finally, to a green colour. On evaporating an aqueous solution to dryness with a few drops of ammonia water, a blue residue is produced which is soluble in alcohol, this solution yielding a red fluorescence on the addition of excess of acetic acid. A few milligrams dissolved in nitric acid gives a yellow solution, which on heating changes to orange and then blood-red, and on evaporation to dryness yields a green residue. This on exposure to the fumes of nitric acid becomes violet-blue, and when a drop of nitric acid is added it forms a reddish-violet solution, which soon changes to blood-red, and finally, on standing or on dilution, becomes greenish-yellow. Sulphuric acid produces a colourless solution, becoming yellow after a time. Sulphuric acid, containing one drop of solution of formaldehyde in each mil, gives a bright pink colour when added to the salt; if sulphuric acid and a few grains of cane sugar be added, a yellow colour is produced, turning to brown, then to purple, and lastly to greenish-black. It is more stable than the other salts of the alkaloid, and is similarly employed, but its sparing solubility in water stands in the way of its more general use.
Soluble in water (1 in 130); alcohol (1 in 12).
Action and Uses.—The action of physostigmine and its salts is described under Physostigminae Sulphas. The salicylate is preferred to the sulphate for the preparation of eye-drops, as its solutions do not so readily become pink in colour. The colouration of solutions of physostigmine salts, due to oxidation, can be prevented by the addition of a trace of boric, hypophosphorous, or sulphurous acid (see Physostigminae Sulphas).
Dose.—1 to 3 milligrams (1/60 to 1/20 grain)