The pancreatic lipase inhibitor, lipstatin, was isolated from Streptomyces in 1987, but because of the 2 unstable cis-double bonds in the structure, Roche has obtained a more stable orlistat by hydrogenation reduction on the premise of retaining its basic structure. It was approved by FDA in 1999 to treat obesity. In addition to having a good weight loss effect, but also can improve the conventional antihypertensive drugs difficult to control the blood pressure of hypertensive patients. In addition, orlistat can control blood sugar and reduce the incidence of diabetes mellitus while weight loss. Orlistat, as a gastrointestinal esterase inhibitor, partially inhibits the lipase of gastric lipase, pancreatic lipase and carboxyl ester, hinders the absorption of fatty acid and single stearic acid in gastrointestinal mucosa cells, thus reducing the absorption of 30% of fat and increasing excretion of feces to achieve the goal of weight loss.
1996 FDA approved the first for long-term treatment of obesity weight loss drug right fentanyl (dexfenfluramine), has a good weight loss efficacy, but because of its 5-ht2b and 5-HT2C receptor is not selective, resulting in serious heart valve lesions, has been withdrawn from the city in 1997. In order to avoid the heart valve adverse reaction caused by the excited 5-HT2B, Arena pharmaceutical company made a structural transformation of the fenfluramine, and the c-1,c-6 of the benzene ring was formed into 1 benzodiazepine nuclei, and then chlorine was substituted for the C-3 bit of trifluoromethyl. Increase its selectivity to 5-ht2c and get Lorcaserin. This product was approved by FDA in June 2012 for use in Body mass index (BMI) ≥27, and at least 1 obese or obese patients with obesity complications of adjuvant therapy. Iorcaserin by selectively activating the 5-HT2C receptor in the hypothalamus, the appetite is reduced, satiety is increased, the inflammatory 5-ht2b is avoided, and the drug safety is enhanced. The most common adverse reactions in patients with non-diabetes were headache, dizziness, fatigue, nausea, dry vomiting and constipation. The most common adverse reactions in diabetics include hypoglycemia, headaches, back pain, cough and fatigue.
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