Synthalin was an oral

anti-diabetic drug Drugs used in diabetes treat diabetes mellitus by altering the glucose level in the blood. With the exceptions of insulin, most GLP receptor agonists ( liraglutide, exenatide, and others), and pramlintide, all are administered orally and are t ...

. Discovered in 1926 it was marketed in Europe by

Schering AG Schering AG was a research-centered German multinational pharmaceutical company headquartered in Wedding, Berlin, which operated as an independent company from 1851 to 2006. In 2006, it was bought by Bayer AG and merged to form the Bayer subsi ...

of Berlin as a synthetic drug with

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabol ...

-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 However, it was toxic to the liver and kidney and was withdrawn from the market in the early 1940s.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 lilac (''Galega officinalis''), was used to treat the symptoms of

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

, and towards the end of the nineteenth century it was discovered to contain

guanidine Guanidine is the compound with the formula HNC(NH2)2. It is a colourless solid that dissolves in polar solvents. It is a strong base that is used in the production of plastics and explosives. It is found in urine predominantly in patients experi ...

. This had a hypoglycaemic effect but was very toxic to the liver.

Karl Slotta Karl Heinrich Slotta (May 12, 1895 in Breslau, Germany (now Wrocław, Poland) – July 17, 1987 in Coral Gables, Florida), was a biochemist. His discovery of progesterone and its relationship to ovulation led to the development of birth contro ...

at the Chemistry Institute of the

University of Vienna The University of Vienna (german: Universität Wien) is a public research university located in Vienna, Austria. It was founded by Duke Rudolph IV in 1365 and is the oldest university in the German-speaking world. With its long and rich h ...

synthesized derived compounds that had a

polymethylene Polyethylene or polythene (abbreviated PE; IUPAC name polyethene or poly(methylene)) is the most commonly produced plastic. It is a polymer, primarily used for packaging ( plastic bags, plastic films, geomembranes and containers includin ...

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 (; 13 January 1858 – 18 July 1931) was a German physician and physiologist who held a professorship at the University of Breslau and is most famous for his research on diabetes. He was the brother of the mathematician Hermann Mi ...

's clinic in Wroclaw performed a clinical 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.

Anti-trypanosome

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 is an antimicrobial medication used to treat African trypanosomiasis, leishmaniasis, '' Balamuthia'' infections, babesiosis, and to prevent and treat pneumocystis pneumonia (PCP) in people with poor immune function. In African trypa ...

is still used against

trypanosomiasis Trypanosomiasis or trypanosomosis is the name of several diseases in vertebrates caused by parasitic protozoan trypanosomes of the genus ''Trypanosoma''. In humans this includes African trypanosomiasis and Chagas disease. A number of other dise ...

. Pentamidine is also effective against a range of protozoa such as ''

Pneumocystis jirovecii ''Pneumocystis jirovecii'' (previously ''P. carinii'') is a yeast-like fungus of the genus ''Pneumocystis''. The causative organism of ''Pneumocystis'' pneumonia, it is an important human pathogen, particularly among immunocompromised hosts. Pr ...

'', which causes

pneumocystis pneumonia ''Pneumocystis'' pneumonia (PCP), also known as ''Pneumocystis jirovecii'' pneumonia (PJP), is a form of pneumonia that is caused by the yeast-like fungus ''Pneumocystis jirovecii''. ''Pneumocystis'' specimens are commonly found in the lungs of ...

in AIDS patients.

References

* * * {{- Guanidines Hepatotoxins Withdrawn drugs