Acipimox Chemical Properties

Melting point:

177-180 °C

Boiling point:

539.0±45.0 °C(Predicted)

Density 

1.44±0.1 g/cm3(Predicted)

storage temp. 

Inert atmosphere,2-8°C

solubility 

Soluble in methanol, water (100 mM), DMSO (100 mM), ethanol (<1 mg/ml at 25° C), and 1 M NH4OH (1 mg/ml).

form 

Solid

pka

2.80±0.10(Predicted)

color 

Yellow

Merck 

14,111

InChIKey

DJQOOSBJCLSSEY-UHFFFAOYSA-N

CAS DataBase Reference

51037-30-0(CAS DataBase Reference)

EPA Substance Registry System

Pyrazinecarboxylic acid, 5-methyl-, 4-oxide (51037-30-0)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36

Safety Statements 

26

WGK Germany 

3

RTECS 

UQ2453000

HS Code 

2933.99.8290

Toxicity

LD50 orally in mice: 3500 mg/kg (Ambrogi)

Acipimox Usage And Synthesis

Description

Acipimox is a nicotinic acid derivate that structurally related to nicotinic acid. Like nicotinic acid, lowers lipids effectively, but unlike nicotinic acid, acipimox is longer acting and therefore much less prone to produce free fatty acid rebounding. It is usually employed in man in the therapy of hypertriglyceridemia. In addition to its lipid lowering activity, it produces a beneficial elevation of the anti-atherogenic high density lipoprotein subfraction, HDL2. Acipimox is recommended as a lipid-lowering agent to treat hyperlipidemia in patients with noninsulin dependent diabetes mellitus.

Chemical Properties

Yellow Solid

Originator

Erbamont (Italy)

Characteristics

The advantages of acipimox to niacin are as follows:
Longer duration of inhibition of hormone-sensitive lipase than niacin.
A lower dose (250 mg BD or TDS) of acipimox is required to lower lipid levels and better tolerability with fewer side effects than niacin.
Acipimox increases insulin sensitivity, while niacin causes insulin resistance. Thus, acipimox has a favorable role in patients with dyslipidemia and diabetes, whereas niacin is contraindicated in diabetes.
Acipimox has adjuvant role in the management of PCOD and increases tissuesensitivity to GH, whereas niacin does not.

Uses

Acipimox is a long-acting antilipemic agent and used for the treatment of hyperlipoproteinemias, in particular hypertriglyceridemias, and as adjunctive therapy for affecting cholesterol metabolism.

Definition

ChEBI: 5-methyl-4-oxido-2-pyrazin-4-iumcarboxylic acid is a pyrazinecarboxylic acid.

Preparation

Synthesis of acipimox: Under cooling and stirring, 78 g of maleic anhydride was dissolved in a solution of 60 ml of chloroform, and 40 ml of 30% hydrogen peroxide was added. After 2 h, 4.8 g of 5-Methyl-2-pyrazinecarboxylic acid was added, and the temperature was kept at 0-5 °C for 2 d. The maleic acid was filtered off. Concentrate to a small volume, add ethyl acetate, and filter to obtain 1.1 g of acipimox, the melting point of which is 178-180 °C.

brand name

OLBETAM

benefits

1. Act on the liver and adipose tissue, inhibit the lipolysis of adipose tissue, thereby reducing plasma total cholesterol, triglyceride, low-density lipoprotein, and very low-density lipoprotein.
2. Increase high-density lipoprotein in plasma, which is beneficial to the transport and clearance of cholesterol.
3. Increase liver glycogen synthesis and lower blood sugar levels. Asimimox can be used as the first-choice lipid-lowering drug for the treatment of various hyperlipidemias, especially for those with diabetes mellitus with hyperlipidemia.

Biological Activity

Acipimox, also known as olbemox, is a nicotinic acid analog. It functions as an anti-lipolytic drug and vasodilator. Acipimox may be used in various metabolic studies involving insulin and ghrelin. It lowers total cholesterol and total triglycerides, which helps in the treatment of hyperlipidemia.

Clinical Use

Acipimox was introduced in Europe to treat hyperlipidemia in 1985. Acipimox is a weak agonist of GPR109A with micromolar binding and functional activity.Like niacin, acipimox raises HDL-C and triggers vasodilation in humans.However, it remains unclear whether acipimox causes mild hyperglycemia as is observed with niacin.

Side effects

Adverse effects include flushing (associated with Prostaglandin D2), rash, palpitations, and GI disturbances (nausea, dyspepsia, diarrhoea and upper abdominal pain) . Flushing can be reduced by taking aspirin 20-30 min before taking Acipimox. High doses can cause disorders of liver function, impair glucose tolerance and precipitate gout.

Drug interactions

Potentially hazardous interactions with other drugs. It can be combined with powerful hypolipidemic drugs such as fenofibrate and lovastatin to enhance the efficacy and reduce the dose and side effects of the drug. Acyclolimus can improve the efficacy of hypoglycemic drugs, so it is necessary to reduce the dose of hypoglycemic drugs and adjust the dose according to the patient's blood sugar. In antioxidant therapy, it can be used in combination with probucol.

Metabolism

Acipimox is not significantly metabolised and is eliminated almost completely intact by the urinary route.

Mode of action

Acipimox is a nicotinic acid derivative (methyl-pyrazine-carboxylic-acid-oxide) that acts on the niacin receptor (GPR109A).The mechanism of action is similar to niacin (inhibition of hormone-sensitive lipase). However，the inhibition of hormone-sensitive lipase by acipimox is remarkably longer (9-12 h) than that of niacin (3 h). Similar to niacin, acipimox also lowers the levels of lp(a).

References

[1] Ana T.M.G. Santomauro, Guenther Boden, Maria E.R. Silva, Dalva M. Rocha, Rosa F. Santos, Mileni J.M. Ursich, Paula G. Strassmann and Bernardo L. Wajchenberg, Overnight Lowering of Free Fatty Acids With Acipimox Improves Insulin Resistance and Glucose Tolerance in Obese Diabetic and Nondiabetic Subjects, Diabetes, 1999, vol. 48, 1836-1841
[2] K. C. Shih, C. F. Kwok, C. M. Hwu, L. C. Hsiao, S. H. Li, Y. F. Liu, L. T. Ho, Acipimox attenuates hypertriglyceridemia in dyslipidemic noninsulin dependent diabetes mellitus patients without perturbation of insulin sensitivity and glycemic control, Diabetes Research and Clinical Practice, 1997, vol. 36, 113-119

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