Meglutol (Dicrotalic acid)

Meglutol is an HMG-CoA reductase inhibitor (IC₅₀ = 4 nM) and antimetabolite of mevalonic acid.¹ Dietary administration of meglutol (10, 20, and 30 mg/kg per day) reduces serum total cholesterol levels in normal rats, as well as reduces them in high-cholesterol fed and hypercholesterolemic rats when administered in the drinking water at a dose of 50 mg/kg per day.² It also reduces serum levels of cholesterol, triglycerides, phospholipids, and free fatty acids, as well as the severity of aortic atherosclerotic lesions, in a rabbit model of atherosclerosis induced by a high-cholesterol diet when administered at a dose of 25 mg/animal per day.³ Intracerebroventricular administration of meglutol (0.5 ?mol/g) induces lipid peroxidation and decreases the activity of glutathione peroxidase in the cerebral cortex of one-day old rat pups.⁴ Meglutol accumulates in the tissues and fluids of patients with HMG-CoA lyase deficiency, a disorder characterized by metabolic acidosis, hypoglycemia, and lethargy.⁴

1.Medina-Franco, J.L., López-Vallejo, F., Rodríguez-Morales, S., et al.Molecular docking of the highly hypolipidemic agent α-asarone with the catalytic portion of HMG-CoA reductaseBioorg. Med. Chem. Lett.15(4)989-994(2005) 2.Beg, Z.H., and Siddiqi, M.Hypocholesterolemic effect of 3-hydroxy-3-methylglutaric acidExperientia23(5)380(1967) 3.Lupien, P.J., Tremblay, M., and Beg, Z.H.3-Hydroxy-3-methylglutaric acid: Protective action in experimental atherosclerosis in rabbitsAtherosclerosis18(3)407-416(1973) 4.da Rosa, M.S., da Rosa-Junior, N.T., Parmeggiani, B., et al.3-Hydroxy-3-methylglutaric acid impairs redox and energy homeostasis, mitochondrial dynamics, and endoplasmic reticulum-mitochondria crosstalk in rat brainNeurotox. Res.37(2)314-325(2020)