Pyramidon

PYRAMIDON, Pyramidonum, Pyrazolonum dimethylamino-phenyldimethylicum, dimethylaminoantipyrine (syn.: amidopyrine, Amidopyrinum) (Pharmacopoeia VII), mol. wt. 231.2. Pyramidon is obtained from antipyrine, which is converted by nitrous acid into isonitrosoantipyrine; reduction of the latter yields aminoantipyrine, which is then methylated. It is a white or slightly yellow crystalline powder, melting at 108°, slowly soluble in 18–20 parts of water, and easily soluble in alcohol. An aqueous solution has a weakly alkaline reaction to litmus; after acidification, it gives a blue-violet color with ferric chloride. Pyramidon has a slightly bitter taste, irritates mucous membranes insignificantly (weaker than antipyrine), is well absorbed by the intestines, and is as a rule completely destroyed in the body. Urine after taking Pyramidon is colored red (more intensely than with antipyrine) due to the presence of rubazonic acid (a pyrazolone derivative). Negligible amounts of undecomposed Pyramidon can be detected in urine by the Jolles reaction: the addition of iodine tincture leads to the appearance of a violet ring, which after some time becomes reddish-brown. Pyramidon was proposed in 1896 by Filehne as an antipyretic and antineuralgic agent, 3–4 times stronger than antipyrine (see). In a healthy person, Pyramidon in a dose of 0.3–0.5 g causes moderate dilation of superficial vessels (mainly vessels of the head) and insignificant sweating; despite the resulting increase in heat dissipation (up to 20–30% above normal), a drop in body temperature does not occur due to a compensatory increase in heat production (Gottlieb). In a febrile patient, Pyramidon causes a more significant increase in heat dissipation with a significant lowering of body temperature, occurring, as with antipyrine and other antipyretics, due to an effect on the abnormally functioning thermoregulation (region of the tuber cinereum). The antipyretic effect of Pyramidon, compared with antipyrine, is distinguished by the fact that it develops more slowly and lasts longer, which represents important therapeutic advantages. The analgesic effect of Pyramidon also has a central origin (region of the optic thalami), and the ability of Pyramidon to dilate vessels (e.g., in migraine) also plays a role in it. Dilation of the vessels of the skin and brain occurs with simultaneous constriction of the vessels of the viscera, which is why blood pressure does not change (and in some cases may increase slightly). Cardiac activity under the influence of Pyramidon hardly changes, and at therapeutic doses, this influence has no significance. With a significant overdose, dizziness, weakness, convulsions, and finally collapse occur. Poisoning of experimental animals is also characterized by convulsive symptoms. Pyramidon (like antipyrine), unlike some other antipyretics, does not alter blood pigment. Side effects and phenomena of idiosyncrasy occur less frequently than with antipyrine. The use of Pyramidon leads to some habituation. Pyramidon is extremely widely used as an antineuralgicum and antipyreticum. Its analgesic effect is so significant that Pyramidon can in many cases replace morphine. Significant improvement in the condition of febrile patients, occurring due to the reduction of temperature, elimination of headaches and other pains, severe malaise, insomnia, etc., gives reason for the frequent use of Pyramidon both in acute febrile diseases (typhus, etc.), especially where hydrotherapeutic procedures are difficult, and in chronic ones (tuberculosis), especially outside hospital or sanatorium settings. Already in the first years of Pyramidon's use, its favorable effect in acute articular rheumatism was discovered (Pauli, Hoffmann, Korovitsky, and others) without Pyramidon being considered particularly indicated for this disease. In recent years, Schottmüller and his clinic have attributed a specific effect to Pyramidon in this disease, in many cases not only not inferior to, but exceeding the effect of salicylic preparations. Schottmüller recommends repeated administration of Pyramidon at 0.3 to 1.5–3.0 per day (i.e., exceeding the maximum daily dose). Pyramidon is also used in fractional doses (0.5:200.0, a tablespoon every 1/2 hour) to lower temperature and eliminate exhausting sweats in tuberculosis patients. A feature of the action of Pyramidon is its property of causing a decrease in temperature only of infectious origin, which gave reason to use it for diagnostic purposes (see Thermoregulation). Finally, Pyramidon is also used as a reagent for blood pigment. Preparations: Pyramidonum (Amidopyrinum)—maximum single dose 0.5, daily 1.5 (Pharmacopoeia VII); Pyramidonum camphoricum—0.5 (0.75); P. bicamphoricum—0.75 (1.0). The latter two preparations were proposed to limit the sweating caused by Pyramidon in febrile patients (action of camphoric acid); P. salicylicum—0.5 (0.75); Citrovanille—a preparation consisting mainly of Pyramidon citrate; Veramon—a combination of Pyramidon with Veronal (0.4–0.6); Compral—a compound of Pyramidon with voluntal. Numerous analogs and combinations have been proposed, such as melubrin (antipyrine-amido-methane-sulfonic acid sodium), novamidon (dimethyl-amino-phenyl-dimethyl-pyrazolone), and many others, but they have not received widespread use in comparison with Pyramidon.

B. Karasik. Detection in forensic cases. Pyramidon is extracted with chloroform from an alkaline solution along with alkaloids. It dissolves in 30 parts of water to form a solution with an alkaline reaction to litmus. Reactions for the detection of Pyramidon are based on its oxidation with the formation of intermediate products colored violet (or blue), which disappear with an excess of reagent. Reactions: 1) ferric chloride gives a violet coloration; 2) nitrous acid (acidified solution of sodium nitrite)—violet coloration; 3) silver nitrate—blue, then precipitation of gray metallic silver.