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Also known as: Fluvastatin sodium salt, 93957-55-2, Lescol, 94061-80-0, Vastin, (3r,5s)-fluvastatin sodium salt
Molecular Formula
C24H25FNNaO4
Molecular Weight
433.4  g/mol
InChI Key
ZGGHKIMDNBDHJB-NRFPMOEYSA-M

Fluvastatin Sodium
An indole-heptanoic acid derivative that inhibits HMG COA REDUCTASE and is used to treat HYPERCHOLESTEROLEMIA. In contrast to other statins, it does not appear to interact with other drugs that inhibit CYP3A4.
1 2D Structure

Fluvastatin Sodium

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
sodium;(E,3R,5S)-7-[3-(4-fluorophenyl)-1-propan-2-ylindol-2-yl]-3,5-dihydroxyhept-6-enoate
2.1.2 InChI
InChI=1S/C24H26FNO4.Na/c1-15(2)26-21-6-4-3-5-20(21)24(16-7-9-17(25)10-8-16)22(26)12-11-18(27)13-19(28)14-23(29)30;/h3-12,15,18-19,27-28H,13-14H2,1-2H3,(H,29,30);/q;+1/p-1/b12-11+;/t18-,19-;/m1./s1
2.1.3 InChI Key
ZGGHKIMDNBDHJB-NRFPMOEYSA-M
2.1.4 Canonical SMILES
CC(C)N1C2=CC=CC=C2C(=C1C=CC(CC(CC(=O)[O-])O)O)C3=CC=C(C=C3)F.[Na+]
2.1.5 Isomeric SMILES
CC(C)N1C2=CC=CC=C2C(=C1/C=C/[C@H](C[C@H](CC(=O)[O-])O)O)C3=CC=C(C=C3)F.[Na+]
2.2 Synonyms
2.2.1 MeSH Synonyms

1. 7-(3-(4-fluorophenyl)-1-(1-methylethyl)-1h-indol-2-yl)-3,5-dihydroxy-6-heptenoate

2. Fluindostatin

3. Fluvastatin

4. Fluvastatin Sodium Salt

5. Lescol

6. Xu 62 320

7. Xu 62-320

8. Xu 62320

9. Xu-62320

10. Xu62320

2.2.2 Depositor-Supplied Synonyms

1. Fluvastatin Sodium Salt

2. 93957-55-2

3. Lescol

4. 94061-80-0

5. Vastin

6. (3r,5s)-fluvastatin Sodium Salt

7. Fluvastatin (sodium)

8. Fluvastatin

9. Canef

10. Sri 62320

11. Sri-62320

12. Fluvastatin Sodium (lescol)

13. (3r,5s)-fluvastatin Sodium

14. Fractal

15. Locol

16. Lescol Xl

17. Sodium (3r,5s,e)-7-(3-(4-fluorophenyl)-1-isopropyl-1h-indol-2-yl)-3,5-dihydroxyhept-6-enoate

18. Sodium;(e,3r,5s)-7-[3-(4-fluorophenyl)-1-propan-2-ylindol-2-yl]-3,5-dihydroxyhept-6-enoate

19. Dsstox_cid_24758

20. Dsstox_rid_80451

21. Dsstox_gsid_44758

22. Lochol

23. Fluvastatin Sodium Hydrate

24. Cranoc

25. Smr000550480

26. Xu-62-320

27. Ab01274723-01

28. Xilep Xl

29. Fluindostatin Sodium

30. Cas-93957-55-2

31. Prestwick_1032

32. Fluyastatin Sodium Salt

33. (+)-fluvastatin Sodium

34. Fluvastatin Sodium,(s)

35. Xu 62320 Sodium

36. Ncgc00164604-01

37. (relative Stereochemistry)

38. Fluvastatin Sodium- Bio-x

39. Schembl41502

40. Mls001165673

41. Mls001304715

42. Mls006010060

43. Chebi:77602

44. Fluvastatin For System Suitability

45. Dtxsid501009854

46. Hms1570l19

47. Hms2233n10

48. (+)-(3r,5s)-fluvastatin Sodium

49. (3r,5s)-(+)-fluvastatin Sodium

50. (3s,5r)-7-(3-(4-fluorophenyl)-1-isopropyl-1h-indol-2-yl)-3,5-dihydroxyhept-6-enoic Acid Sodium Salt

51. Tox21_112226

52. Hy-14664a

53. Mfcd00929076

54. S1909

55. Xu-620

56. Akos016340657

57. Tox21_112226_1

58. Ac-6856

59. Ccg-264930

60. Cs-1969

61. Ks-1062

62. Ncgc00263525-01

63. (3r,5s)-7-[3-(4-fluorophenyl)-1-(1-methylethyl)-1h-indol-2-yl]-3,5-dihydroxy-6-heptenoic Acid Sodium Salt

64. Bf164477

65. Sw197104-2

66. H11964

67. A844750

68. Q27147203

69. (3r,5s,6e)-7-[3-(4-fluorophenyl)-1-(1-methylethyl)-1h-indol-2-yl]-3,5-dihydroxy-6-heptenoic Acid

70. (3r,5s,6e)-7-[3-(4-fluorophenyl)-1-isopropyl-1h-indol-2-yl]-3,5-dihydroxy Hept-6-enoic Acid Sodium Salt

71. (3r,5s,6e)-7-[3-(4-fluorophenyl)-1-isopropyl-1h-indol-2-yl]-3,5-dihydroxyhept-6-enoic Acid Sodium Salt

72. (3s,5r)-rel-7-[3-(4-fluorophenyl)-1-isopropyl-1h-indol-2-yl]-3,5-dihydroxyhept-6-enoic Acid Sodium Salt

73. (e)-(3r,5s)-(+)-7-[3-(4-fluoro-phenyl)-1-isopropyl-1h-indol-2-yl]-3,5-dihydroxy-hept-6-enoic Acid Sodium Salt

74. (e)-(3r,5s)-7-[3-(4-fluoro-phenyl)-1-isopropyl-1h-indol-2-yl]-3,5-dihydroxy-hept-6-enoic Acid Sodium Salt

75. (e)-(3r,5s)-7-[3-(4-fluoro-phenyl)-1-isopropyl-1h-indol-2-yl]-3,5-dihydroxy-hept-6enoic Acid Sodium Salt

76. 6-heptenoic Acid, 7-(3-(4-fluorophenyl)-1-(1-methylethyl)-1h-indol-2-yl)-3,5-dihydroxy-, Monosodium Salt, (s-(r*,s*-(e)))-

77. Sodium (3r,5s,6e)-7-[3-(4-fluorophenyl)-1-isopropyl-1h-indol-2-yl]-3,5-dihydroxyhept-6-enoate

78. Sodium (e)-(3r,5s)-7-[3-(4-fluoro-phenyl)-1-isopropyl-1h-indol-2-yl]-3,5-dihydroxy-hept-6-enoate

79. Sodium 7-[3-(4-fluorophenyl)-1-isopropyl-indol-2-yl]-3,5-dihydroxy-hept-6-enoate;fluvastatin Sodium

80. Sodium(3r,5s,e)-7-(3-(4-fluorophenyl)-1-isopropyl-1h-indol-2-yl)-3,5-dihydroxyhept-6-enoate

2.3 Create Date
2008-02-05
3 Chemical and Physical Properties
Molecular Weight 433.4 g/mol
Molecular Formula C24H25FNNaO4
Hydrogen Bond Donor Count2
Hydrogen Bond Acceptor Count5
Rotatable Bond Count8
Exact Mass433.16653072 g/mol
Monoisotopic Mass433.16653072 g/mol
Topological Polar Surface Area85.5 Ų
Heavy Atom Count31
Formal Charge0
Complexity596
Isotope Atom Count0
Defined Atom Stereocenter Count2
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count1
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count2
4 Drug and Medication Information
4.1 Drug Information
1 of 6  
Drug NameFluvastatin sodium
PubMed HealthFluvastatin (By mouth)
Drug ClassesAntihyperlipidemic
Drug LabelLescol (fluvastatin sodium), is a water-soluble cholesterol lowering agent which acts through the inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Fluvastatin sodium is [R*,S*-(E)]-()-7-[3-(4-fluorophenyl)-1-(1-m...
Active IngredientFluvastatin sodium
Dosage FormTablet, extended release; Capsule
Routeoral; Oral
Strengtheq 20mg base; eq 40mg base; 80mg
Market StatusTentative Approval; Prescription
CompanyMylan Pharms; Par Pharm; Teva Pharms

2 of 6  
Drug NameLescol
PubMed HealthFluvastatin (By mouth)
Drug ClassesAntihyperlipidemic
Drug LabelLescol (fluvastatin sodium), is a water-soluble cholesterol lowering agent which acts through the inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Fluvastatin sodium is [R*,S*-(E)]-()-7-[3-(4-fluorophenyl)-1-(1-m...
Active IngredientFluvastatin sodium
Dosage FormCapsule
RouteOral
Strengtheq 20mg base; eq 40mg base
Market StatusPrescription
CompanyNovartis

3 of 6  
Drug NameLescol xl
Drug LabelLescol (fluvastatin sodium), is a water-soluble cholesterol lowering agent which acts through the inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Fluvastatin sodium is [R*,S*-(E)]-()-7-[3-(4-fluorophenyl)-1-(1-m...
Active IngredientFluvastatin sodium
Dosage FormTablet, extended release
RouteOral
Strength80mg
Market StatusPrescription
CompanyNovartis

4 of 6  
Drug NameFluvastatin sodium
PubMed HealthFluvastatin (By mouth)
Drug ClassesAntihyperlipidemic
Drug LabelLescol (fluvastatin sodium), is a water-soluble cholesterol lowering agent which acts through the inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Fluvastatin sodium is [R*,S*-(E)]-()-7-[3-(4-fluorophenyl)-1-(1-m...
Active IngredientFluvastatin sodium
Dosage FormTablet, extended release; Capsule
Routeoral; Oral
Strengtheq 20mg base; eq 40mg base; 80mg
Market StatusTentative Approval; Prescription
CompanyMylan Pharms; Par Pharm; Teva Pharms

5 of 6  
Drug NameLescol
PubMed HealthFluvastatin (By mouth)
Drug ClassesAntihyperlipidemic
Drug LabelLescol (fluvastatin sodium), is a water-soluble cholesterol lowering agent which acts through the inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Fluvastatin sodium is [R*,S*-(E)]-()-7-[3-(4-fluorophenyl)-1-(1-m...
Active IngredientFluvastatin sodium
Dosage FormCapsule
RouteOral
Strengtheq 20mg base; eq 40mg base
Market StatusPrescription
CompanyNovartis

6 of 6  
Drug NameLescol xl
Drug LabelLescol (fluvastatin sodium), is a water-soluble cholesterol lowering agent which acts through the inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Fluvastatin sodium is [R*,S*-(E)]-()-7-[3-(4-fluorophenyl)-1-(1-m...
Active IngredientFluvastatin sodium
Dosage FormTablet, extended release
RouteOral
Strength80mg
Market StatusPrescription
CompanyNovartis

4.2 Therapeutic Uses

Anticholesteremic Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors

National Library of Medicine's Medical Subject Headings. Fluvastatin. Online file (MeSH, 2016). Available from, as of November 1, 2016: https://www.nlm.nih.gov/mesh/2016/mesh_browser/MBrowser.html


Fluvastatin capsules are indicated: as an adjunct to diet to reduce elevated total cholesterol (Total-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and apolipoprotein B (Apo B) levels, and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson Type IIa and IIb); As an adjunct to diet to reduce Total-C, LDL-C, and Apo B levels in adolescent boys and adolescent girls who are at least one year post-menarche, 10 to 16 years of age, with heterozygous familial hypercholesterolemia and the following findings are present: 1. LDL-C remains >/= 190 mg/dL or 2. LDL-C remains >/= 160 mg/dL and: there is a positive family history of premature cardiovascular disease or two or more other cardiovascular disease risk factors are present. /Included in US product label/

NIH; DailyMed. Current Medication Information for Fluvastatin Tablet (Updated: March 2016). Available from, as of November 4, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aad8b373-0aec-4efb-8e61-3d8114b31127#i4i_section_id_5f2eb94b-4cdf-4517-9ad8-298e02fe9677


In patients with clinically evident coronary heart disease (CHD), fluvastatin capsules are indicated to: reduce the risk of undergoing coronary revascularization procedures and slow the progression of coronary atherosclerosis. /Included in US product label/

NIH; DailyMed. Current Medication Information for Fluvastatin Tablet (Updated: March 2016). Available from, as of November 4, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aad8b373-0aec-4efb-8e61-3d8114b31127#i4i_section_id_5f2eb94b-4cdf-4517-9ad8-298e02fe9677


Fluvastatin has reduced total and LDL-cholesterol concentrations in a few patients with hypercholesterolemia associated with or exacerbated by diabetes mellitus (diabetic dyslipidemia), renal insufficiency,cardiac or renal transplantation, or nephrotic syndrome (nephrotic hyperlipidemia). Fluvastatin also has been shown to decrease proteinuria in patients with immunoglobulin A nephropathy. Additional studies are necessary to determine the role, if any, of fluvastatin therapy in patients with these disorders. /NOT included in US product label/

American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 1849


4.3 Drug Warning

Rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with fluvastatin capsules and other drugs in this class.

NIH; DailyMed. Current Medication Information for Fluvastatin Tablet (Updated: March 2016). Available from, as of November 4, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aad8b373-0aec-4efb-8e61-3d8114b31127#i4i_section_id_5f2eb94b-4cdf-4517-9ad8-298e02fe9677


There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including fluvastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with fluvastatin sodium, promptly interrupt therapy. If an alternate etiology is not found do not restart fluvastatin sodium.

NIH; DailyMed. Current Medication Information for Fluvastatin Tablet (Updated: March 2016). Available from, as of November 4, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aad8b373-0aec-4efb-8e61-3d8114b31127#i4i_section_id_5f2eb94b-4cdf-4517-9ad8-298e02fe9677


Fluvastatin is secreted into the breast milk of animals and because HMG-CoA reductase inhibitors have the potential to cause serious adverse reactions in nursing infants, women who require treatment with fluvastatin capsules should be advised not to breastfeed their infants.

NIH; DailyMed. Current Medication Information for Fluvastatin Tablet (Updated: March 2016). Available from, as of November 4, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aad8b373-0aec-4efb-8e61-3d8114b31127#i4i_section_id_5f2eb94b-4cdf-4517-9ad8-298e02fe9677


Fluvastatin capsules are contraindicated in women who are pregnant or may become pregnant. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Fluvastatin capsules may cause fetal harm when administered to pregnant women. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. Fluvastatin capsules should be administered to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards. If the patient becomes pregnant while taking this drug, fluvastatin capsules should be discontinued and the patient should be apprised of the potential hazard to the fetus.

NIH; DailyMed. Current Medication Information for Fluvastatin Tablet (Updated: March 2016). Available from, as of November 4, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aad8b373-0aec-4efb-8e61-3d8114b31127#i4i_section_id_5f2eb94b-4cdf-4517-9ad8-298e02fe9677


For more Drug Warnings (Complete) data for Fluvastatin (24 total), please visit the HSDB record page.


5 Pharmacology and Biochemistry
5.1 FDA Pharmacological Classification
5.1.1 Pharmacological Classes
Hydroxymethylglutaryl-CoA Reductase Inhibitors [MoA]; HMG-CoA Reductase Inhibitor [EPC]
5.2 ATC Code

C - Cardiovascular system

C10 - Lipid modifying agents

C10A - Lipid modifying agents, plain

C10AA - Hmg coa reductase inhibitors

C10AA04 - Fluvastatin


5.3 Absorption, Distribution and Excretion

/MILK/ Based on animal data, fluvastatin is present in breast milk in a 2:1 ratio (milk:plasma).

NIH; DailyMed. Current Medication Information for Fluvastatin Tablet (Updated: March 2016). Available from, as of November 4, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aad8b373-0aec-4efb-8e61-3d8114b31127#i4i_section_id_5f2eb94b-4cdf-4517-9ad8-298e02fe9677


Following oral administration of the capsule, fluvastatin reaches peak concentrations in less than 1 hour. The absolute bioavailability is 24% (range 9% to 50%) after administration of a 10 mg dose.

NIH; DailyMed. Current Medication Information for Fluvastatin Tablet (Updated: March 2016). Available from, as of November 4, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aad8b373-0aec-4efb-8e61-3d8114b31127#i4i_section_id_5f2eb94b-4cdf-4517-9ad8-298e02fe9677


Fluvastatin is 98% bound to plasma proteins. The mean volume of distribution (VDss) is estimated at 0.35 L/kg. At therapeutic concentrations, the protein binding of fluvastatin is not affected by warfarin, salicylic acid and glyburide.

NIH; DailyMed. Current Medication Information for Fluvastatin Tablet (Updated: March 2016). Available from, as of November 4, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aad8b373-0aec-4efb-8e61-3d8114b31127#i4i_section_id_5f2eb94b-4cdf-4517-9ad8-298e02fe9677


Fluvastatin administered as fluvastatin sodium extended-release 80 mg tablets reaches peak concentration in approximately 3 hours under fasting conditions, after a low fat meal, or 2.5 hours after a low fat meal. The mean relative bioavailability of the extended-release tablet is approximately 29% (range: 9% to 66%) compared to that of the fluvastatin immediate-release capsule administered under fasting conditions. Administration of a high fat meal delayed the absorption (Tmax: 6 hr) and increased the bioavailability of the extended-release tablet by approximately 50%. However, the maximum concentration of fluvastatin sodium extended-release tablets seen after a high fat meal is less than the peak concentration following a single dose or twice daily dose of the 40 mg fluvastatin capsule.

NIH; DailyMed. Current Medication Information for Fluvastatin Tablet (Updated: March 2016). Available from, as of November 4, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aad8b373-0aec-4efb-8e61-3d8114b31127#i4i_section_id_5f2eb94b-4cdf-4517-9ad8-298e02fe9677


For more Absorption, Distribution and Excretion (Complete) data for Fluvastatin (8 total), please visit the HSDB record page.


5.4 Metabolism/Metabolites

In vitro data indicate that fluvastatin metabolism involves multiple Cytochrome P450 (CYP) isozymes. CYP2C9 isoenzyme is primarily involved in the metabolism of fluvastatin (approximately 75%), while CYP2C8 and CYP3A4 isoenzymes are involved to a much less extent, i.e., approximately 5% and approximately 20%, respectively.

NIH; DailyMed. Current Medication Information for Fluvastatin Tablet (Updated: March 2016). Available from, as of November 4, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aad8b373-0aec-4efb-8e61-3d8114b31127#i4i_section_id_5f2eb94b-4cdf-4517-9ad8-298e02fe9677


Fluvastatin is metabolized in the liver, primarily via hydroxylation of the indole ring at the 5 and 6 positions. N-dealkylation and beta-oxidation of the side-chain also occurs. The hydroxy metabolites have some pharmacologic activity, but do not circulate in the blood. Fluvastatin has two enantiomers. Both enantiomers of fluvastatin are metabolized in a similar manner.

NIH; DailyMed. Current Medication Information for Fluvastatin Tablet (Updated: March 2016). Available from, as of November 4, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aad8b373-0aec-4efb-8e61-3d8114b31127#i4i_section_id_5f2eb94b-4cdf-4517-9ad8-298e02fe9677


5.5 Biological Half-Life

The elimination half-life of fluvastatin is approximately 3 hours.

NIH; DailyMed. Current Medication Information for Fluvastatin Tablet (Updated: March 2016). Available from, as of November 4, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aad8b373-0aec-4efb-8e61-3d8114b31127#i4i_section_id_5f2eb94b-4cdf-4517-9ad8-298e02fe9677


5.6 Mechanism of Action

Fluvastatin sodium is a competitive inhibitor of HMG-CoA reductase, the rate limiting enzyme that converts 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate, a precursor of sterols, including cholesterol. The inhibition of cholesterol biosynthesis reduces the cholesterol in hepatic cells, which stimulates the synthesis of LDL receptors and thereby increases the uptake of LDL particles. The end result of these biochemical processes is a reduction of the plasma cholesterol concentration.

NIH; DailyMed. Current Medication Information for Fluvastatin Tablet (Updated: March 2016). Available from, as of November 4, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aad8b373-0aec-4efb-8e61-3d8114b31127#i4i_section_id_5f2eb94b-4cdf-4517-9ad8-298e02fe9677


Statins are largely used in clinics in the treatment of patients with cardiovascular diseases for their effect on lowering circulating cholesterol. Lectin-like oxidized low-density lipoprotein (LOX-1), the primary receptor for ox-LDL, plays a central role in the pathogenesis of atherosclerosis and cardiovascular disorders. We have recently shown that chronic exposure of cells to lovastatin disrupts LOX-1 receptor cluster distribution in plasma membranes, leading to a marked loss of LOX-1 function. Here we investigated the molecular mechanism of statin-mediated LOX-1 inhibition and we demonstrate that all tested statins /including fluvastatin/ are able to displace the binding of fluorescent ox-LDL to LOX-1 by a direct interaction with LOX-1 receptors in a cell-based binding assay. Molecular docking simulations confirm the interaction and indicate that statins completely fill the hydrophobic tunnel that crosses the C-type lectin-like (CTLD) recognition domain of LOX-1. Classical molecular dynamics simulation technique applied to the LOX-1 CTLD, considered in the entire receptor structure with or without a statin ligand inside the tunnel, indicates that the presence of a ligand largely increases the dimer stability. Electrophoretic separation and western blot confirm that different statins binding stabilize the dimer assembly of LOX-1 receptors in vivo. The simulative and experimental results allow us to propose a CTLD clamp motion, which enables the receptor-substrate coupling. These findings reveal a novel and significant functional effect of statins.

PMID:25950192 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614984 Biocca S et al; Cell Cycle 14 (10): 1583-95 (2015)


Epidemiological studies suggest that statins (hydroxymethylglutaryl-CoA reductase inhibitors) could reduce the risk of Alzheimer disease. Although one possible explanation is through an effect on beta-amyloid (Abeta) metabolism, its effect remains to be elucidated. Here, we explored the molecular mechanisms of how statins influence Abeta metabolism. Fluvastatin at clinical doses significantly reduced Abeta and amyloid precursor protein C-terminal fragment (APP-CTF) levels among APP metabolites in the brain of C57BL/6 mice. Chronic intracerebroventricular infusion of lysosomal inhibitors blocked these effects, indicating that up-regulation of the lysosomal degradation of endogenous APP-CTFs is involved in reduced Abeta production. Biochemical analysis suggested that this was mediated by enhanced trafficking of APP-CTFs from endosomes to lysosomes, associated with marked changes of Rab proteins, which regulate endosomal function. In primary neurons, fluvastatin enhanced the degradation of APP-CTFs through an isoprenoid-dependent mechanism. Because our previous study suggests additive effects of fluvastatin on Abeta metabolism, we examined Abeta clearance rates by using the brain efflux index method and found its increased rates at high Abeta levels from brain. As LRP1 in brain microvessels was increased, up-regulation of LRP1-mediated Abeta clearance at the blood-brain barrier might be involved. In cultured brain microvessel endothelial cells, fluvastatin increased LRP1 and the uptake of Abeta, which was blocked by LRP1 antagonists, through an isoprenoid-dependent mechanism. Overall, the present study demonstrated that fluvastatin reduced Abeta level by an isoprenoid-dependent mechanism. ...

PMID:20472556 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903370 Shinohara M et al; J Biol Chem 285 (29): 22091-102 (2010)


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27-Jan-2021
30-Oct-2024
KGS
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