Ethyl eicosapentaenoic acid

Ethyl eicosapentaenoic acid

200px
Names
IUPAC name Ethyl (5Z,8Z,11Z,14Z,17Z)-eicosa-5,8,11,14,17-pentaenoate
Other names Eicosapentaenoic acid ethyl ester; Ethyl eicosapentaenoate; Eicosapent; ; EPA ethyl ester; E-EPA;
Identifiers
CAS Number	86227-47-6 Y
ChEBI	CHEBI:84883 N
ChemSpider	8007147 N
IUPHAR/BPS	7441
Jmol 3D model	Interactive image
PubChem	9831415
InChI InChI=1S/C22H34O2/c1-3-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-22(23)24-4-2/h5-6,8-9,11-12,14-15,17-18H,3-4,7,10,13,16,19-21H2,1-2H3/b6-5-,9-8-,12-11-,15-14-,18-17- N Key: SSQPWTVBQMWLSZ-AAQCHOMXSA-N N InChI=1/C22H34O2/c1-3-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-22(23)24-4-2/h5-6,8-9,11-12,14-15,17-18H,3-4,7,10,13,16,19-21H2,1-2H3/b6-5-,9-8-,12-11-,15-14-,18-17- Key: SSQPWTVBQMWLSZ-AAQCHOMXBQ
SMILES CC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CCCC(=O)OCC
Properties
Chemical formula	C22H34O2
Molar mass	330.51 g·mol−1
Vapor pressure	{{{value}}}
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Infobox references

Ethyl eicosapentaenoic acid (E-EPA) marketed as Vascepa, Epadel, EPAX, is a synthetic derivative of the omega-3 fatty acid eicosapentaenoic acid (EPA). In Japan, E-EPA is often called EPA-E.

This compound has been FDA-approved for use for reduction of high triglyceride levels. E-EPA may exhibit antipsychotic and antidepressive effects, and it is therefore of special interest in psychiatry.

Cardiovascular diseases, diabetes

The Japan Eicosapentaenoic acid Lipid Intervention Study (JELIS) tested the effects of long-term use of E-EPA (1800 mg/day) in addition to a statin in Japanese patients with hypercholesterolemia. The results suggest that the addition of E-EPA to statin therapy prevents major coronary events, angina pectoris and clinical myocardial infarctions, apparently through mechanisms independent from regulation of the lipid metabolism. It has been suggested that the cardioprotective action of E-EPA is probably mediated by its anti-inflammatory properties. In addition, E-EPA may improve the clinical outcome in type 2 diabetes and its cardiovascular complications, such as coronary artery disease and thickening of carotid arteries. E-EPA may on the one hand reduce the platelet-derived microparticles (PDMP) and on the other enhance the cardioprotective hormone adiponectin in hyperlipidemic, diabetic patients. According to Japanese mice studies, E-EPA may prevent and correct non-alcoholic fatty liver. In July 2012, the US Food and Drug Administration approved Amarin Corporation's prescription drug Vascepa for severe hypertriglyceridemia.

Mental health

Acute psychosis

As adjuct therapy, E-EPA has been tested in first-episode psychosis. The daily dosage of E-EPA given in these trials, i.e., 2 gram per day, corresponds to 10 to 15 helpings of Atlantic salmon.

In schizophrenia, the trials are based on the so-called membrane theory of the disease. According to the Omega-3 Subcommittee of the American Psychiatric Association (APA), the evidence of the effects is still too weak to recommend the use of E-EPA, but more studies are currently in progress.

Clinical depression

Omega-3 fatty acids have been investigated as adjunct therapy for depression as they are anti-inflammatory agents and chronic low-grade inflammation has been linked to clinical depression. Moreover, omega-3 content in the cell membranes of depressive persons is often decreased, and supplementation with omega-3 may correct this deficiency and improve the clinical outcome. This hypothesis has been tested in a number of clinical trials using E-EPA, mostly 1 gram daily.

Most (but not all) trials have yielded positive results. In one study E-EPA boosted the effect of an antidepressive drug, fluoxetine. According to a December 2009 report from Massachusetts General Hospital in Boston, E-EPA seems to be more effective than placebo as monotherapy in major depressive disorder.

Bipolar depression

The first placebo-controlled study with omega-3 fatty acid ethyl esters, mainly EPA ethyl ester and DHA ethyl ester, filled softgels obtained from the NIH's Fish Oil Test Materials Program was carried out at Harvard University by professor Andrew L. Stoll, published in 1999. His team later demonstrated that rigid cell membranes in test subjects were smoothed by omega-3 fatty acids. Subsequent studies at King's College London's Institute of Psychiatry have demonstrated the efficacy of E-EPA in bipolar patients. One of the biochemical mechanisms appears to be enhancement of an amino acid called N-acetyl aspartate (NAA) in the brain. E-EPA seems to exert similar effect on the NAA concentration as lithium which has been used for bipolar depression for decades.

Borderline personality disorder

In 2003, there was an 8-week, placebo-controlled, double-blind study of E-EPA in 30 women that met Revised Diagnostic Interview for Borderlines and DSM-IV criteria for borderline personality disorder (BPD). Results of this study implied that E-EPA may be a safe and effective form of monotherapy for women with moderately severe BPD.

Psychological stress

Animal tests demonstrate that E-EPA balances the metabolism of glucocorticoids (cortisol and cortisone) and may thus alleviate stress symptoms and attenuate interleukin 1-beta (IL-1b) induced changes in dopamine and its metabolites in the shell of the nucleus accumbens. The fatty acid EPA may confer neuroprotection in the amyloid-β challenged aged hippocampus.

Side effects

The most common reported adverse reaction (incidence >2% and greater than placebo) was arthralgia (joint pain).

Other conditions

E-EPA has been tested and found beneficial in anorexia nervosa, hepatitis C, in children with ulcerative colitis, nonalcoholic fatty liver (steatohepatitis), in psychological stress in postmenopausal middle-aged women, and in women suffering from menopausal hot flushes.

See also

• Eicosapentaenoic acid (EPA)

Safety aspects

E-EPA 2 g/day is generally well tolerated. Clinicians should be aware of possible increases in bleeding time, as well as changes in weight and lipid metabolism.

External links

• Function of E-EPA on the nerve cell membrane. Animation
• Icosapent bound to proteins in the PDB

• Horrobin D. The Madness of Adam and Eve. How schizophrenia shaped humanity. Bantam Press 2001
• King A. Does treatment with eicosapentaenoic acid prevent major coronary events in patients with hypercholesterolemia? Editorial. Commentary by William S. Harris Nat Clin Pract Cardiovasc Med. 2007 Aug 14; Free Full Text
• as PDF
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• Peet M. Essential fatty acids: theoretical aspects and treatment implications for schizophrenia and depression. Advances in Psychiatric Treatment (2002) 8: 223-229 Free Full Text
• as PDF
• Full Free Text
• Clinical Trials
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• http://bjp.rcpsych.org/content/188/1/46.long
• http://www.boston.com/2011/08/25/docdiscipline/LmzzCsfIvBgJLSosVU2HKM/story.html
• Frangou S, Lewis M, Wollard J, Simmons A. Preliminary in vivo evidence of increased N-acetyl-aspartate following eicosapentanoic acid treatment in patients with bipolar disorder. J Psychopharmacol. 2006 Aug 4 Free Full Text
• as PDF
• http://www.vascepa.com/hcp/multiple-lipids.shtml
• http://investor.amarincorp.com
• http://www.vascepa.com/side-effects.shtml
• https://www.vascepa.com
• as PDF
• as PDF