Сурамин: Африка ұйықтамасы мен өзен соқырлығына қарсы дәрі

Medical drug

Suramin is a medication used to treat African sleeping sickness and river blindness. Suramin causes a fair number of side effects. Suramin was made at least as early as 1916. It is on the World Health Organization's List of Essential Medicines. In the United States it can be acquired from the Centers for Disease Control (CDC). In regions of the world where the disease is common suramin is provided for free by the World Health Organization (WHO).

Suramin is used for treatment of human sleeping sickness caused by trypanosomes. It has been used in the treatment of river blindness (onchocerciasis). Suramin can also cause loss of appetite and irritability.

Suramin is not orally bioavailable and must be given intravenously. Intramuscular and subcutaneous administration could result in local tissue inflammation or necrosis Suramin is approximately 99 98% protein bound in the serum and has a half life of 41–78 days average of 50 days; however, the pharmacokinetics of suramin can vary substantially between individual patients. Suramin does not distribute well into cerebral spinal fluid and its concentration in the tissues is equivalently lower than its concentration in the plasma. Suramin is not extensively metabolized and about 80% is eliminated via the kidneys. The synthesis of suramin itself and structural analogs is by successive formation of the amide bonds from their corresponding amine (aniline) and carboxyl (as acyl chloride) components. Various routes to these compounds have been developed, including starting from separate naphthalene structures and building towards an eventual unification by formation of the urea or starting with a urea and appending successive groups.

The mechanism of action for suramin is unclear, but it is thought that parasites are able to selectively uptake suramin via receptor mediated endocytosis of drug that is bound to low density lipoproteins and, to a lesser extent, other serum proteins.

Suramin was first made by the chemists Oskar Dressel, Richard Kothe and Bernhard Heymann at Bayer AG laboratories in Elberfeld, after research on a series of urea like compounds. The drug is still sold by Bayer under the brand name Germanin. The chemical structure of suramin was kept secret by Bayer for commercial and strategic reasons, but it was elucidated and published in 1924 by Ernest Fourneau and his team at the Pasteur Institute.

It is also used as a research reagent to inhibit the activation of heterotrimeric G proteins in a variety of GPCRs with varying potency. It prevents the association of heteromeric G proteins and therefore the receptors guanine exchange functionality (GEF). With this blockade the GDP will not release from the Gα subunit so it can not be replaced by a GTP and become activated. This has the effect of blocking downstream G protein mediated signaling of various GPCR proteins including rhodopsin, the A1 adenosine receptor, the D2 receptor, the P2 receptor, and ryanodine receptors. Suramin was studied as a possible treatment for prostate cancer in a clinical trial. Suramin has been studied in a mouse model of autism and in a small phase I/II human trial. Results from a randomized clinical study found no statistically significant effects of suramin (in either 10mg or 20mg doses) versus placebo on boys with moderate to severe autism spectrum disorder. Suramin is a reversible and competitive protein tyrosine phosphatase (PTPases) inhibitor, also is the potent inhibitor of sirtuins, purified topoisomerase II and SARS CoV 2 RNA dependent RNA polymerase (RdRp).