Synthalin
Encyclopedia
Synthalin was an oral anti-diabetic drug
. Discovered in 1926 it was marketed in Europe by Schering AG of Berlin as a synthetic drug with insulin
-like properties that could be taken orally. However, it was toxic to the liver and kidney and was withdrawn from the market in the early 1940s.
(Galega officinalis), was used to treat the symptoms of diabetes, and towards the end of the nineteenth century it was discovered to contain guanidine
. This had an hypoglycaemic effect but was very toxic to the liver. Karl Slotta at the Chemistry Institute of the University of Vienna
synthesied derived compounds that had a polymethylene chain with a guanidine group at each end. These diguanides were less toxic and more potent than guanidine. In 1926, E. Frank, working in Oskar Minkowski
's clinic in Breslau performed a clinicial trial on one of these agents. It was subsequently marketed as Synthalin by Schering AG for treating mild cases of diabetes.
Adverse reports on the toxicity of Synthalin prompted the development of Synthalin B (which had a slightly longer polymethylene chain and was claimed to be safer) and the former product was re-branded Synthalin A. However liver toxicity continued to be a problem, leading to discontinuation in the 1930s, though Synthalin B continued to be used in Germany until the mid 1940s.
After it was discovered that trypanosomes require a plentiful supply of glucose in order to reproduce, researchers tested Synthalin and related compounds to see if they could be effective treatments. Synthalin was effective, at doses lower than would interfere with blood sugar in the patient. Further modifications to the chemical structure led to the diamidine class of drugs, of which pentamidine
is still used against trypanosomiasis
. Pentamidine is also effective against a range of protozoa such as pneumocystis jirovecii, which causes pneumocystis pneumonia
in AIDS
patients.
Anti-diabetic drug
Anti-diabetic medications treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents...
. Discovered in 1926 it was marketed in Europe by Schering AG of Berlin as a synthetic drug with insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
-like properties that could be taken orally. However, it was toxic to the liver and kidney and was withdrawn from the market in the early 1940s.
History
The folk remedy French lilacGalega officinalis
Galega officinalis, commonly known as goat's rue, French lilac, Italian fitch or professor-weed, is an herbaceous plant in the Faboideae subfamily. It is native to the Middle East, but it has been naturalised in Europe, western Asia, and western Pakistan...
(Galega officinalis), was used to treat the symptoms of diabetes, and towards the end of the nineteenth century it was discovered to contain guanidine
Guanidine
Guanidine is a crystalline compound of strong alkalinity formed by the oxidation of guanine. It is used in the manufacture of plastics and explosives. It is found in urine as a normal product of protein metabolism. The molecule was first synthesized in 1861 by the oxidative degradation of an...
. This had an hypoglycaemic effect but was very toxic to the liver. Karl Slotta at the Chemistry Institute of the University of Vienna
University of Vienna
The University of Vienna is a public university located in Vienna, Austria. It was founded by Duke Rudolph IV in 1365 and is the oldest university in the German-speaking world...
synthesied derived compounds that had a polymethylene chain with a guanidine group at each end. These diguanides were less toxic and more potent than guanidine. In 1926, E. Frank, working in Oskar Minkowski
Oskar Minkowski
Oskar Minkowski He held a professor at at the University of Breslau and is most famous for his research on diabetes...
's clinic in Breslau performed a clinicial trial on one of these agents. It was subsequently marketed as Synthalin by Schering AG for treating mild cases of diabetes.
Adverse reports on the toxicity of Synthalin prompted the development of Synthalin B (which had a slightly longer polymethylene chain and was claimed to be safer) and the former product was re-branded Synthalin A. However liver toxicity continued to be a problem, leading to discontinuation in the 1930s, though Synthalin B continued to be used in Germany until the mid 1940s.
After it was discovered that trypanosomes require a plentiful supply of glucose in order to reproduce, researchers tested Synthalin and related compounds to see if they could be effective treatments. Synthalin was effective, at doses lower than would interfere with blood sugar in the patient. Further modifications to the chemical structure led to the diamidine class of drugs, of which pentamidine
Pentamidine
Pentamidine is an antimicrobial medication given for prevention and treatment of Pneumocystis pneumonia caused by Pneumocystis jirovecii , a severe interstitial type of pneumonia often seen in patients with HIV infection...
is still used against trypanosomiasis
Trypanosomiasis
Trypanosomiasis or trypanosomosis is the name of several diseases in vertebrates caused by parasitic protozoan trypanosomes of the genus Trypanosoma. Approximately 500,000 men, women and children in 36 countries of sub-Saharan Africa suffer from human African trypanosomiasis which is caused by...
. Pentamidine is also effective against a range of protozoa such as pneumocystis jirovecii, which causes pneumocystis pneumonia
Pneumocystis pneumonia
Pneumocystis pneumonia or pneumocystosis is a form of pneumonia, caused by the yeast-like fungus Pneumocystis jirovecii...
in AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
patients.