Buformin Systematic (IUPAC) name N-butylimidocarbonimidic diamide Clinical data AHFS/Drugs.com International Drug Names Pregnancy cat. ? Legal status Withdrawn in most countries, still available in Japan, Taiwan, and Hungary Routes Oral Pharmacokinetic data Excretion Renal Identifiers CAS number 692-13-7 ATC code A10BA03 PubChem CID 2468 DrugBank DB04830 ChemSpider 2374 UNII W2115E9C7B KEGG D00595 ChEMBL CHEMBL39736 Chemical data Formula C6H15N5 Mol. mass 157.217 g/mol SMILES eMolecules & PubChem (what is this?) (verify)
Buformin (1-butylbiguanide) is an oral anti-diabetic drug of the biguanide class, chemically related to metformin and phenformin. Buformin was marketed by German pharmaceutical company Grünenthal as Silubin.
Chemistry and Animal Toxicology
Buformin hydrochloride is a fine white to slightly yellow crystalline powder, odorless, with a weakly acidic bitter taste, melting point 174° to 177°, strong base, freely soluble in water, methanol and ethanol, insoluble in chloroform and ether. Toxicity: guinea pig LD50 subcutaneous 18mg/kg; mouse LD50 intraperitoneal 140mg/kg and 300mg/kg oral. Partition coefficient: log P (octanol-water) -1.20E+00; Water Solubility 7.46E+05 mg/L at 25°. Vapor pressure 1.64E-04 mm Hg at 25° (EST); Henry's Law Constant 8.14E-16 atm-m3/mole at 25° (EST). Atmospheric OH Rate Constant 1.60E-10 cm3/molecule-sec at 25°
Mechanism of Action
Buformin delays absorption of glucose from the gastrointestinal tract, increases insulin sensitivity and glucose uptake into cells and inhibits synthesis of glucose by the liver. Buformin and the other biguanides are not hypoglycemic, but rather anti-hyperglycemic agents. They do not produce hypoglycemia; instead, they reduce basal and postprandial hyperglycemia in diabetics. 
After oral administration of 50 mg of buformin to volunteers, almost 90% of the applied quantity was recovered in the urine; the rate constant of elimination was found to be 0.38 hr-1. Buformin is a strong base (pKA = 11.3) and not absorbed in the stomach. After i.v. injection of about 1 mg/kg buformin-14-C, the initial serum concentration is 0.2-0.4 µg/ml. Serum level and urinary elimination rate are linearly correlated.  In man, after oral administration of 50 mg 14-C-buformin, the maximum serum concentration was 0.26-0.41 µg/ml. The buformin was eliminated with an average half-life of 2 h. 84% of the dose administered was found excreted unchanged in the urine.  Buformin is not metabolized in man.
The daily dose of buformin is 150-300 mg by mouth. Buformin has also been available in a sustained release preparation.
Anorexia; nausea; diarrhea; metallic taste; weight loss.
Diabetic coma; ketoacidosis; severe infection; trauma; other severe infections where buformin is unlikely to control the hyperglycemia; renal or hepatic impairment; heart failure; recent myocardial infarct; dehydration; alcoholism; conditions likely to predispose to lactic acidosis.
Buformin was withdrawn from the market in most countries due to an elevated risk of causing lactic acidosis, but is still available and prescribed in Hungary,  Taiwan,  and Japan.  The lactic acidosis occurred only in patients with a buformin plasma level of greater than 0.60 µg/ml and was rare in patients with normal renal function.  In one report the toxic oral dose was 329 ± 30mg/day in 24 patients who developed lactic acidosis on buformin. Another group of 24 patients on 258 ± 25mg/day did not develop lactic acidosis on buformin.
Buformin, along with Phenformin and Metformin, inhibits the growth and development of cancer.  The anti-cancer property of these drugs is due to their ability to disrupt the Warburg effect and revert the cytosolic glycolysis characteristic of cancer cells to normal oxidation of pyruvate by the mitochondria. Metformin reduces liver glucose production in diabetics and disrupts the Warburg effect in cancer by AMPK activation and inhibition of the mTor pathway. 
Buformin was synthesized as an oral antidiabetic in 1957.
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- ^ Matthew G. Vander Heiden, Lewis C. Cantley, and Craig B. Thompson. Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation. Science 324 (5930): 1029-1033, 2009.
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- ^ Seymour L. Shapiro et al. Salts Of N-Amylbiguanide. US Patent number: 2961377; Filing date: Aug 5, 1957; Issue date: 1960
Oral anti-diabetic drugs and Insulin analogs (A10) InsulinMetformin# • Buformin‡ • Phenformin‡Aleglitazar† • Muraglitazar§ • Tesaglitazar§K+ ATPMeglitinides/"glinides"GLP-1 analogsExenatide • Liraglutide • Taspoglutide† • Albiglutide† • LixisenatideAnalogs/other insulinsfast-acting (Insulin lispro • Insulin aspart • Insulin glulisine) • short-acting (Regular insulin) • long-acting (Insulin glargine • Insulin detemir • NPH insulin) • ultra-long-acting (Insulin degludec†) • inhalable Exubera‡ OtherAmylin analogSGLT2 inhibitorsCanagliflozin† • Dapagliflozin† • Remogliflozin§ • Sergliflozin§OtherBenfluorex‡ • Tolrestat‡#WHO-EM. ‡Withdrawn from market. Clinical trials: †Phase III. §Never to phase IIICategories:
- Withdrawn drugs
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