Promin, or sodium glucosulfone is a

sulfone In organic chemistry, a sulfone is a organosulfur compound containing a sulfonyl () functional group attached to two carbon atoms. The central hexavalent sulfur atom is double-bonded to each of two oxygen atoms and has a single bond to each of ...

drug that was investigated for the treatment of

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. ...

tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, ...

and

leprosy Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria '' Mycobacterium leprae'' or '' Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve d ...

. It is broken down in the body to

dapsone Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS), is an antibiotic commonly used in combination with rifampicin and clofazimine for the treatment of leprosy. It is a second-line medication for the treatment a ...

, which is the therapeutic form.

History

The first synthesis of Promin is sometimes credited to Edward Tillitson and B.F. Tuller of Parke, Davis, & Co. pharmaceuticals in August 1937. However, although Parke-Davis did in fact synthesize the compound, it seems certain that they were not the first; in cooperation with J. Wittmann, Emil Fromm synthesised various sulfone compounds in 1908, including both dapsone and some of its derivatives, such as promin. Fromm and Wittmann however were engaged on chemical rather than medical work, and no-one investigated the medical value of such compounds until some decades afterwards. The medical evaluation of sulfones was inspired by the discovery of the unprecedented value of synthetic compounds such as sulfonamides in treating microbial diseases. Early investigations yielded disappointing results, but subsequently promin and dapsone proved valuable in treating mycobacterial diseases. They were the first treatments to show more than a glimmer of hope of controlling such infections.< Initially, Promin appeared to be safer than dapsone, so it was further investigated at the

Mayo Clinic The Mayo Clinic () is a nonprofit American academic medical center focused on integrated health care, education, and research. It employs over 4,500 physicians and scientists, along with another 58,400 administrative and allied health staf ...

as a treatment for tuberculosis in a

guinea pig The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy (), is a species of rodent belonging to the genus '' Cavia'' in the family Caviidae. Breeders tend to use the word ''cavy'' to describe the ...

model. Because it was already known that leprosy and tuberculosis were both caused by mycobacteria (''

Mycobacterium leprae ''Mycobacterium leprae'' (also known as the leprosy bacillus or Hansen's bacillus), is one of the two species of bacteria that cause Hansen’s disease (leprosy), a chronic but curable infectious disease that damages the peripheral nerves an ...

'' and ''

Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on it ...

'', respectively), Guy Henry Faget of the National Leprosarium in Carville, Louisiana, requested information about the drug from Parke-Davis. They, in turn, informed him of the work being done on leprosy in rats by Edmund Cowdry at the

Washington University School of Medicine Washington University School of Medicine (WUSM) is the medical school of Washington University in St. Louis in St. Louis, Missouri. Founded in 1891, the School of Medicine has 1,260 students, 604 of which are pursuing a medical degree with ...

. His successful results, published in 1941, convinced Faget to begin human studies, both with promin and

sulfoxone Sulfoxone or aldesulfone sodium is an anti-leprosy drug. It is also known as diasone. Sulfoxone sodium was introduced in Japan in 1948. Ernest Muir introduced it to Western use while serving as superintendent of the Chacachacare Leprosarium on Tr ...

sodium, a related compound from

Abbott Laboratories Abbott Laboratories is an American multinational medical devices and health care company with headquarters in Abbott Park, Illinois, United States. The company was founded by Chicago physician Wallace Calvin Abbott in 1888 to formulate known dr ...

. The initial trials were on six volunteers, and were then expanded and replicated in different locations. Despite severe side effects that caused the initial tests to be suspended temporarily, the drug was shown to be effective. This breakthrough was reported worldwide, and led to a reduction in the stigma attached to leprosy, and consequent better treatment of patients, at the time still referred to as "inmates", and forbidden from using public transport.

Pharmacology

Promin is heat-stable and water-soluble, and can therefore be heat-sterilized. It can be injected intravenously, and is available in ampules. Beyond its solubility, however, promin was later found to have no real advantages over the simpler compound dapsone (which is administered in tablet form). Promin and other sulfones can also not be used as substitutes for dapsone when intolerance develops, as this is a general reaction to sulfones, and not specific to dapsone. Today, the drugs of choice for treating leprosy are dapsone,

rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. It is almost always used t ...

and

clofazimine Clofazimine, sold under the brand name Lamprene, is a medication used together with rifampicin and dapsone to treat leprosy. It is specifically used for multibacillary (MB) leprosy and erythema nodosum leprosum. Evidence is insufficient to suppor ...

References

{{Antimycobacterials Anilines Benzosulfones Dihydropteroate synthetase inhibitors Antileprotic drugs Prodrugs