tolbutamidiin

Tolbutamide is a first‑generation sulfonylurea drug that was discovered in the late 1950s and introduced into clinical practice in the early 1960s as a treatment for type II diabetes mellitus. It is a small, lipophilic molecule that belongs to the class of compounds characterized by a sulfonylurea functional group linked to aromatic rings. The drug is administered orally in tablet form and has a half‑life of approximately 5–10 hours, though its antidiabetic effect can last longer due to its activity on pancreatic β‑cells.

The mechanism of action of tolbutamide involves binding to receptors on the pancreatic β‑islet cell membrane, which triggers the closing of ATP‑sensitive potassium channels. This depolarizes the cell membrane, opens voltage‑gated calcium channels, and leads to a rise in intracellular calcium concentration. The subsequent influx promotes the exocytosis of insulin granules, thereby increasing plasma insulin levels and reducing blood glucose concentration. Tolbutamide primarily stimulates insulin release from pre‑existing pancreatic reserves and is therefore less effective in patients with severe β‑cell dysfunction.

Common adverse reactions include hypoglycaemia, weight gain, and gastrointestinal upset such as nausea, vomiting, and diarrhoea. Less frequently, skin rashes or allergic reactions may occur. Tolbutamide has largely been supplanted by newer, better‑tolerated sulfonylureas such as glipizide, glyburide, and glimepiride, but it remains part of the historical pharmacology of antihyperglycaemic agents.