Oct. 09, 2021
Epalrestat is a carboxylic acid derivative and a non-competitive and reversible aldose reductase inhibitor used to treat diabetic neuropathy, one of the most common long-term complications in diabetic patients. It reduces the accumulation of intracellular sorbitol, which is believed to be responsible for diabetic neuropathy, retinopathy and nephropathy.
Epalrestat 150 mg/day for 12 weeks improved motor and sensory nerve conduction velocities and vibration thresholds in patients with diabetic neuropathy compared to baseline and placebo. Subjective symptoms including pain, numbness, sensory hypersensitivity, chills in the extremities, muscle weakness, dizziness and upright syncope were also improved. Similar benefits were seen in comparisons with historical controls. Epalrestat 300 mg/day for 1 or 3 years was also significantly better than placebo or no treatment in improving electroretinographic parameters and time to recovery from light stress in patients with diabetic retinopathy. Improvements were also documented by fundoscopy and fluorescein angiography.
Chemically, epalrestat is unusual in that it is a rhodanine containing group. Aldose reductase is a key enzyme in the polyol pathway and its increased activity underlies diabetic neuropathy. Aldose reductase inhibitors (ARIs) target this enzyme. Of the many ARIs in development, ranirestat and fidarestat are in the trial phase. Epalrestat is the only commercially available ARI that is readily absorbed into the nerve tissue and inhibits the enzyme with minimal side effects.
At the same time, Alpha-methyl cinnamaldehyde CAS 1199-77-5 is also an important intermediate for the synthesis of the therapeutic drug epalrestat. As the number of diabetic patients increases, the demand for the drug increases, and the demand for α-methyl cinnamaldehyde intermediates also increases, and there is an urgent need to improve the process to improve quality.
Animal studies have demonstrated improvements in sorbitol levels and Na+/K+ ATPase activity, resulting in increased nerve conduction velocity. Diabetic rats treated with epalrestat exhibited improved nerve morphological abnormalities. In a placebo-controlled double-blind trial in 196 patients, a dose of 150 mg/day of epalrestat was demonstrated to improve the effects of diabetic neuropathy such as spontaneous pain in the upper limbs, motor nerve conduction velocity, Vibro-sensory thresholds and autonomic nerve function compared to placebo. These effects were significantly better in those with poorly controlled diabetes. Epalrestat has shown some benefit in the control of diabetic cardiovascular autonomic neuropathy.
Alpha-methyl cinnamaldehyde of Molecular Formula
The sorbitol (polyol) metabolic pathway is an alternative glucose reduction pathway involving aldose reductase and sorbitol dehydrogenase and is thought to be activated by hyperglycaemic conditions. Intracellular accumulation of sorbitol during hyperglycaemia is thought to be at least partially responsible for the pathogenesis of delayed complications of diabetes. Epalrestat, a non-competitive aldose reductase inhibitor, significantly reduced intracellular sorbitol accumulation in the sciatic nerve, red blood cell and eye tissue in animal models and in human red blood cells with diabetes, without affecting glucose levels. Epalrestat also increased the uptake of sodium-dependent inositol in rat sciatic nerve tissue and in skin fibroblasts from diabetic patients.
The recommended dose is epalrestat 50 mg, taken orally three times daily before meals.
Epalrestat is specifically recommended for patients with high glycosylated haemoglobin levels (indicating failure to control hyperglycaemia) despite standard pharmacological and non-pharmacological interventions.
Wuhan LANDMARK Industrial Co., Ltd., as a leading alpha-methyl cinnamic acid manufacturer, supplier, and exporter in China, is a comprehensive high-tech enterprise integrating scientific research, production, and sales. It specializes in the production of cinnamon products, including cinnamic acid and cinnamaldehyde, Cinnamyl alcohol, methyl cinnamate, ethyl cinnamate, etc. We can also accept customization of other cinnamon derivatives. Welcome to contact us to send the catalog!