Aminophenazone (or aminopyrine, amidopyrine, Pyramidon) is a non-narcotic

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

substance. It is a

pyrazolone Pyrazolone is 5-membered heterocycle containing two adjacent nitrogen atoms. It can be viewed as a derivative of pyrazole possessing an additional carbonyl (C=O) group. Compounds containing this functional group are useful commercially in analgesic ...

and a derivative of

phenazone Phenazone (INN and BAN; also known as phenazon, antipyrine (USAN), or analgesine) is an analgesic (pain reducing), antipyretic (fever reducing) and anti-inflammatory drug. While it predates the term, it is often classified as a nonsteroidal anti- ...

, which also has anti-inflammatory and

antipyretic An antipyretic (, from ''anti-'' 'against' and ' 'feverish') is a substance that reduces fever. Antipyretics cause the hypothalamus to override a prostaglandin-induced increase in temperature. The body then works to lower the temperature, which r ...

properties. While inexpensive and effective, especially in the treatment of

rheumatism Rheumatism or rheumatic disorders are conditions causing chronic, often intermittent pain affecting the joints or connective tissue. Rheumatism does not designate any specific disorder, but covers at least 200 different conditions, including art ...

, the drug carries a serious risk of severe and sometimes fatal side-effects, including

agranulocytosis Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing a neutropenia in the circulating blood. ...

. While its production and use have been banned in many countries, including France, Thailand, India and Japan, it is still sometimes used in the developing world. A breath test with ¹³C-labeled aminopyrine has been used as a non-invasive measure of

cytochrome Cytochromes are redox-active proteins containing a heme, with a central Fe atom at its core, as a cofactor. They are involved in electron transport chain and redox catalysis. They are classified according to the type of heme and its mode of bin ...

P-450 metabolic activity in liver-function tests. It is also used in measuring the total body water in the human body system.

History

Aminophenazone was first synthesized by

Friedrich Stolz Friedrich Stolz (6 April 1860 – 2 April 1936) was a German chemist and, in 1904, the first person to artificially synthesize epinephrine (adrenaline). References

* 1860 births 1936 deaths 19th-century German chemists 20th-century Ger ...

and

Ludwig Knorr Ludwig Knorr (2 December 1859 – 4 June 1921) was a German chemist. Together with Carl Paal, he discovered the Paal–Knorr synthesis, and the Knorr quinoline synthesis and Knorr pyrrole synthesis are also named after him. The synthesis in 18 ...

in the late nineteenth century, and sold as an anti-fever medicine known as Pyramidon by

Hoechst AG Hoechst AG () was a German chemicals then life-sciences company that became Aventis Deutschland after its merger with France's Rhône-Poulenc S.A. in 1999. With the new company's 2004 merger with Sanofi-Synthélabo, it became a subsidiary of the ...

from 1897 until its eventual replacement by the safer

propyphenazone Propyphenazone (known as isopropylantipyrine in Japan) is a derivative of phenazone with similar analgesic and antipyretic effects. Originally patented in 1931, propyphenazone is marketed as a combination formulation with paracetamol and caffein ...

molecule.

Symptoms

Symptoms of exposure to this compound include: * allergic reactions * strong spasmolytic effect on smooth muscle of peripheral blood vessels * irritability *

palsy Palsy is a medical term which refers to various types of paralysisDan Agin, ''More Than Genes: What Science Can Tell Us About Toxic Chemicals, Development, and the Risk to Our Children;; (2009), p. 172. or paresis, often accompanied by weakness and ...

* copious sweating * dilated pupils * sharp drop then rise in body temperature *

dysuria Dysuria refers to painful or uncomfortable urination. It is one of a constellation of ''irritative'' bladder symptoms (also sometimes referred to as lower urinary tract symptoms), which includes nocturia and urinary frequency. Diagnosis The clin ...

dyspnea Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathing, breathe well enough. The American Thoracic Society defines it as "a subjective experience of brea ...

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

rectal tenesmus Rectal tenesmus is a feeling of incomplete defecation. It is the sensation of inability or difficulty to empty the bowel at defecation, even if the bowel contents have already been evacuated. Tenesmus indicates the feeling of a residue, and is not ...

* urinary frequency * intermittent fever * fatty infiltration of the liver * heart muscle degeneration * death due to circulatory failure following

cardiovascular collapse Shock is the state of insufficient blood flow to the tissues of the body as a result of problems with the circulatory system. Initial symptoms of shock may include weakness, fast heart rate, fast breathing, sweating, anxiety, and increased thi ...

Agranulocytosis Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing a neutropenia in the circulating blood. ...

often occurs. Ingestion may cause central nervous system stimulation, vomiting, convulsions,

cyanosis Cyanosis is the change of body tissue color to a bluish-purple hue as a result of having decreased amounts of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Body tissues that show cyanosis are usually in locations ...

tinnitus Tinnitus is the perception of sound when no corresponding external sound is present. Nearly everyone experiences a faint "normal tinnitus" in a completely quiet room; but it is of concern only if it is bothersome, interferes with normal hearin ...

leukopenia Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of inf ...

, kidney damage and coma. Ingestion may also lead to nausea, mental disturbances,

methemoglobinemia Methemoglobinemia, or methaemoglobinaemia, is a condition of elevated methemoglobin in the blood. Symptoms may include headache, dizziness, shortness of breath, nausea, poor muscle coordination, and blue-colored skin (cyanosis). Complications m ...

, chocolate-colored blood, dizziness, epigastric pain, difficulty in hearing, thready pulse and liver damage. Other symptoms reported via ingestion include

hemolytic anemia Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly ...

porphyria Porphyria is a group of liver disorders in which substances called porphyrins build up in the body, negatively affecting the skin or nervous system. The types that affect the nervous system are also known as acute porphyria, as symptoms are ra ...

and severe gastrointestinal bleeding.

Bone marrow depression Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (t ...

also occurs. Rare eye effects include acute transient myopia. Chronic symptoms include: *

anorexia Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...

oliguria Oliguria or hypouresis is the low output of urine specifically more than 80 ml/day but less than 400ml/day.Boon et al, Davidson's Principles & Practice of Medicine (20th Ed), p475 The decreased output of urine may be a sign of dehydration, kidney ...

urticaria Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...

* hypersensitivity *

aplastic anemia Aplastic anemia is a cancer in which the body fails to make blood cells in sufficient numbers. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood ...

* sore throat * fever * pharyngeal membrane * jaundice enlargement of the liver and spleen * exfoliative dermatitis * gastric or duodenal erosion with perforation or bleeding * adrenal

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...

thrombocytopenic purpura Thrombocytopenic purpura are purpura associated with a reduction in circulating blood platelets which can result from a variety of causes, such as kaposi sarcoma. Types By tradition, the term idiopathic thrombocytopenic purpura is used when the ...

* acute

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

When heated to decomposition this compound emits toxic fumes of

nitrogen oxide Nitrogen oxide may refer to a binary compound of oxygen and nitrogen, or a mixture of such compounds: Charge-neutral *Nitric oxide (NO), nitrogen(II) oxide, or nitrogen monoxide *Nitrogen dioxide (), nitrogen(IV) oxide * Nitrogen trioxide (), or n ...

Metabolism

Amidopyrine is metabolized by demethylation and acetylation. Amidopirina metabolites are 4-aminoantipyrine, metilaminoantipirin, rubazonovaya and metilrubazonovaya acid. These acids have a reddish color. At high amidopirine doses, urine can have a reddish brown coloration, due to the presence in the urine of these acid markers.

References

Pyrazolones Analgesics Antipyretics Nonsteroidal anti-inflammatory drugs {{analgesic-stub