Sulfonylureas
Sulphonylureas are oral anti-diabetic drugs , drugs that are used in type 2 diabetes mellitus (diabetes). They enable the increased release of insulin by blocking potassium channels in the β-cells of the pancreas . They are structurally related to the sulfonamides . Some sulfonylureas are also effective as herbicides .
Use as an antidiabetic agent
pharmacology
Sulphonylureas stimulate the release of insulin from the β-cells of the pancreas regardless of the blood glucose concentration (insulinotropic effect). They block the ATP-sensitive potassium channels of the β-cell by binding to specific SUR-1 binding sites. As a result of the depolarization of the cell, voltage-gated calcium channels open. The calcium influx leads to an emptying of the insulin from the storage vesicles and thus to an increased release of insulin into the blood. They are effective in reducing the risk of microvascular events ( glibenclamide ). Gliquidon is the only member of the sulfonylureas group that is only broken down by the liver and can therefore be given in cases of renal insufficiency .
The first antidiabetic drugs based on sulfonylureas came onto the market around 1956, the development at Boehringer Mannheim under Erich Haack (and previously his developments at the pharmaceutical company von Heyden in Radebeul), which led to Oranil ( carbutamide , clinical tests Hellmuth Kleinsorge ), was important, however, several other drugs came onto the market at about the same time. The blood sugar lowering effect of sulfonamides was first noted in France by Auguste Loubatières in the 1930s . The blood sugar lowering effect was initially seen as a disturbing side effect of the main antibiotic effect.
Side effects
Sulphonylureas can lead to hypoglycaemia , possibly also to gastrointestinal complaints. They promote weight gain through the antilipolytic effects of insulin. Rare side effects are blood formation disorders or hepatic cholestasis (as with sulfonamides ).
Sulphonylureas force insulin to be released from the β-cells of the pancreas, which can lead to hypoglycaemia . Furthermore, studies indicate that sulfonylureas can lead to a failure of the β-cells.
According to the latest studies, sulfonylureas can pose cardiac risks.
Contraindications
Sulphonylureas and their derivatives are contraindicated in diabetes mellitus type 1, severe liver or kidney failure (this does not apply to gliquidone and repaglinide) and pancreatectomy. During pregnancy , diabetics must be switched to insulin . Further contraindications exist in the case of major surgical interventions or severe infections.
Representative
The best-known representative is glibenclamide. Glimepiride has a longer duration of action than glibenclamide. Older, much weaker sulfonylureas are tolbutamide and carbutamide.
First generation sulfonylureas:
Second generation sulfonylureas:
- Glibenclamid (trade names for example Euglucon N , Normoglucon , Glucobe and Dia-Eptal )
- Glibornurid (Gluborid, Glutril)
- Gliclazid (trade name Diamicron UNO )
- Glipizid (Glibenese, Minidiab)
- Gliquidon (Glurenorm)
- Glisoxepid (Pro-Diaban)
- Glycodiazine (Redul)
Third generation sulfonylureas:
- Glimepirid (trade name for example Amaryl )
Use as a herbicide
The sulfonylureas (SU) are one of the most important groups of herbicides. In 2010 over 30% of the German cereal-growing areas were treated with them.
The introduction of sulfonylureas led to a reduction in the application rates from around 2000 g · ha −1 to 3–60 g · ha −1 . This level is still unsurpassed today.
Compared to other classes of herbicide active ingredients (growth substances, triazines, ACCase inhibitors), sulfonylureas have a wide range of effects.
The sulfonylureas are weakly acidic. Depending on the pH, they are either anion or neutral. At room temperature they are crystalline solids with extremely low vapor pressure, which is why dry formulations are ideal. Many sulfonylurea herbicides are formulated as water-dispersible granules (WG).
Due to their highly specific mechanism of action as an inhibitor of acetolactate synthase , the sulfonylureas are at risk of resistance through point mutations of the target enzyme.
| Surname | Area of application: selectivity for |
Application rate in g · ha −1 | Manufacturer |
|---|---|---|---|
| Amidosulfuron | Grain | 30-60 | Bayer CropScience |
| Azimsulfuron | rice | DuPont | |
| Bensulfuron-methyl | rice | 20-75 | DuPont |
| Chlorimuron-ethyl | Soybeans | 8-13 | DuPont |
| Chlorsulfuron | Grain | 9-25 | DuPont |
| Cinosulfuron | rice | 20-40 | Syngenta |
| Cyclosulfamuron | |||
| Ethametsulfuron-methyl | Rapeseed | 15-20 | DuPont |
| Ethoxysulfuron | |||
| Flazasulfuron | Fruit, wine, non-cultivated land | 15-20 | Ishihara |
| Foramsulfuron | |||
| Flupyrsulfuron-methyl- Na | Grain (especially against field foxtail, wind stalk) |
||
| Halosulfuron-methyl | Corn, grassland | 18-25 | Nissan |
| Imazosulfuron | Rice, grassland | 50-100 | Takeda |
| Iodosulfuron | |||
| Mesosulfuron | Grain (especially against field foxtail) |
||
| Metsulfuron-methyl | Grain, rice non-cultivated land |
3-8 14-168 |
DuPont |
| Nicosulfuron | Corn | 35-70 | DuPont / Ishihara |
| Oxasulfuron | |||
| Primisulfuron-methyl | Corn | 20-40 | Syngenta |
| Prosulfuron | Grain, corn | 20-40 | Syngenta |
| Pyrazosulfuron-ethyl | rice | 15-30 | Nissan |
| Rimsulfuron | Potatoes, corn | 5-25 | DuPont |
| Sulfometuron-methyl | Non-cultivated land, forest | 26-420 | DuPont |
| Sulfosulfuron | Grain (especially against brusque, couch grass, wind stalk) |
Monsanto | |
| Thifensulfuron-methyl | Grassland | 2-30 | DuPont |
| Triasulfuron | Grain | 10-30 | Syngenta |
| Tribenuron-methyl | Grain | 9-18 | DuPont |
| Trifloxysulfuron sodium | |||
| Triflusulfuron-methyl | Beets | 15-30 | DuPont |
Individual evidence
- ↑ S. Matthaei et al.: Medicinal antihyperglycemic therapy of type 2 diabetes mellitus (PDF; 815 kB), In: Diabetology. 4, 2009, pp. 32-64.
- ↑ Onmeda: Sulphonylureas ( page no longer available , search in web archives ) Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.
- ^ Richard K. Bernstein: Dr. Bernstein's Diabetes Solution . 1997, ISBN 0-316-09906-6 , pp. 225 .
- ↑ YN Chen, SY Chen, LJ Zeng, JM Ran, MY Wu: Progressive decrease of proinsulin secretion in sulphonylurea-treated type 2 diabetes. In: Br J Biomed Sci. 62 (1), 2005, pp. 5-8. PMID 15816204 .
- ↑ A. Takahashi, K. Nagashima, A. Hamasaki, N. Kuwamura, Y. Kawasaki, H. Ikeda, Y. Yamada, N. Inagaki, Y. Seino: Sulfonylurea and glinide reduce insulin content, functional expression of K (ATP ) channels, and accelerate apoptotic beta-cell death in the chronic phase. In: Diabetes Res Clin Pract. 77 (3), Sep 2007, pp. 343-350. Epub 2007 Feb 20. PMID 17316868 .
- ↑ Type 2 diabetes mellitus: cardiac risks of sulfonylureas. In: Deutsches Ärzteblatt. December 4, 2009. Study on this: Ioanna Tzoulaki, Mariam Molokhia et al .: Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. In: BMJ. 339, 2009, p. B4731.
- ↑ Klaus Aktories (ed.): Special and general pharmacology and toxicology. 9th edition. Urban & Fischer, 2005, ISBN 3-437-42521-8 .
- ↑ a b c d e Hans G. Drobny, Martin Schulte, Harry J. Strek: 25 years of sulfonylurea herbicides - a few grams changed the world of chemical weed control . In: Julius Kühn Archive . tape 434 , 2012, p. 21–33 , doi : 10.5073 / jka.2012.434.002 ( PDF ).
- ↑ a b Modern Crop Protection Compounds. Chapter 2: Acetohydroxyacid Synthase Inhibitors (AHAS / ALS). doi: 10.1002 / 9783527619580.ch2
- ↑ Instructions for use Monitor ( Memento of the original from March 4, 2016 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.
