ACIPIMOX

Details

Stereochemistry	ACHIRAL
Molecular Formula	C6H6N2O3
Molecular Weight	154.1234
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CN=C(C=[N+]1[O-])C(O)=O

InChI

InChIKey=DJQOOSBJCLSSEY-UHFFFAOYSA-N

InChI=1S/C6H6N2O3/c1-4-2-7-5(6(9)10)3-8(4)11/h2-3H,1H3,(H,9,10)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7438693 | https://www.ncbi.nlm.nih.gov/pubmed/8720602 | https://www.medicines.org.uk/emc/medicine/5355 | https://www.ncbi.nlm.nih.gov/pubmed/12522134 | https://www.ncbi.nlm.nih.gov/pubmed/12646212

Acipimox (5-methylpyrazinecarboxylic acid 4-oxide) is a new lipolysis inhibitor that has a distant chemical relationship with nicotinic acid (NA). The anti-lipolytic action of acipimox is mediated through suppression of intracellular cyclic AMP levels, with the subsequent decrease in cyclic AMP-dependent protein kinase activity, leading to the reduced association of hormone-sensitive lipase with triacylglycerol substrate in the lipid droplet of adipocytes. Acipimox has been identified as an agonist at G-protein coupled nicotinic acid HM74A and HM74B receptors. Acipimox (Olbetam) is indicated for the treatment as alternative or adjunct treatment to reduce triglyceride levels in patients who have not responded adequately to other treatments such as statin or fibrate treatment for hypertriglyceridaemia (Fredrickson type IV hyperlipoproteinaemia) and hypercholesterolaemia and hypertriglyceridaemia (Fredrickson type IIb hyperlipoproteinaemia).

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Hydroxycarboxylic acid receptor 2 32 Target ID: CHEMBL3785 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12522134	Agonist 2678	6.0 µM [EC50]
lipid catabolic process 1 Target ID: GO:0016042 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7438693 \| https://www.ncbi.nlm.nih.gov/pubmed/8720602	Inhibitor 8297
HM74 nicotinic acid GPCR 17 Target ID: CHEMBL4421 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12646212	Agonist 2678	4.39 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hyperlipoproteinemia type IV 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1914867 http://adisinsight.springer.com/drugs/800050700	Primary		Approved 8429	OLBETAM Approved Use Olbetam is indicated as alternative or adjunct treatment to reduce triglyceride levels in patients who have not responded adequately to other treatments such as statin or fibrate treatment for: • hypertriglyceridaemia (Fredrickson type IV hyperlipoproteinaemia); • hypercholesterolaemia and hypertriglyceridaemia (Fredrickson type IIb hyperlipoproteinaemia). Olbetam should be used after other measures have been taken such as dietary changes and other non-pharmacological treatment (e.g. exercise, weight reduction). It has not been shown that treatment of hyperlipoproteinaemia with acipimox leads to a reduction of cardiac morbidity or mortality.
Hyperlipoproteinemia type IIb 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1914867 http://adisinsight.springer.com/drugs/800050700	Primary		Approved 8429	OLBETAM Approved Use Olbetam is indicated as alternative or adjunct treatment to reduce triglyceride levels in patients who have not responded adequately to other treatments such as statin or fibrate treatment for: • hypertriglyceridaemia (Fredrickson type IV hyperlipoproteinaemia); • hypercholesterolaemia and hypertriglyceridaemia (Fredrickson type IIb hyperlipoproteinaemia). Olbetam should be used after other measures have been taken such as dietary changes and other non-pharmacological treatment (e.g. exercise, weight reduction). It has not been shown that treatment of hyperlipoproteinaemia with acipimox leads to a reduction of cardiac morbidity or mortality.

PubMed

Title	Date	PubMed
18F-fluorodeoxyglucose accumulation in the heart, brain and skeletal muscle of rats; the influence of time after injection, depressed lipid metabolism and glucose-insulin.	2001	14600964
Lowering plasma free fatty acids with Acipimox mimics the antidiabetic effects of the beta 3-adrenergic agonist CL-316243 in obese Zucker diabetic fatty rats.	2001 Aug	11474483
Inhibition of the rise in FFA by Acipimox partially prevents GH-induced insulin resistance in GH-deficient adults.	2001 Dec	11739444
Reducing plasma free fatty acids by acipimox improves glucose tolerance in high-fat fed mice.	2001 Feb	11350276
Characterization of a G protein-coupled receptor for nicotinic acid.	2001 Feb	11160872
Short-term Acipimox decreases the ability of plasma from Type 2 diabetic patients and healthy subjects to stimulate cellular cholesterol efflux: a potentially adverse effect on reverse cholesterol transport.	2001 Jun	11472472
Metabolic and endocrine consequences of acute suppression of FFAs by acipimox in polycystic ovary syndrome.	2001 Nov	11701699
Effects of fatty acids on exercise plus insulin-induced glucose utilization in trained and sedentary subjects.	2002 Jan	11739092
Mechanisms of leptin secretion from white adipocytes.	2002 Jul	12055093
Comparison between insulin tolerance test, growth hormone (GH)-releasing hormone (GHRH), GHRH plus acipimox and GHRH plus GH-releasing peptide-6 for the diagnosis of adult GH deficiency in normal subjects, obese and hypopituitary patients.	2003 Aug	12887288
Effect of diabetes mellitus on myocardial 18F-FDG SPECT using acipimox for the assessment of myocardial viability.	2003 Jun	12791813
Molecular identification of nicotinic acid receptor.	2003 Mar 28	12646212
Pharmacotherapy for dyslipidaemia--current therapies and future agents.	2003 Nov	14596646
Effect of acute reduction of free fatty acids by acipimox on growth hormone-releasing hormone-induced GH secretion in type 1 diabetic patients.	2003 Oct	14510904
Effect of beta1- and beta2-adrenergic stimulation on energy expenditure, substrate oxidation, and UCP3 expression in humans.	2003 Oct	12824081
The decisive role of free fatty acids for protein conservation during fasting in humans with and without growth hormone.	2003 Sep	12970312
High-fat diet elevates resting intramuscular triglyceride concentration and whole body lipolysis during exercise.	2004 Feb	14559721
Statin use and cancer risk in the General Practice Research Database.	2004 Feb 9	14760377
Anti-aging effects of anti-lipolytic drugs.	2004 Jul	15236765
Modulation of basal glucose metabolism and insulin sensitivity by growth hormone and free fatty acids during short-term fasting.	2004 Jun	15191347
Plasma adiponectin is modestly decreased during 24-hour insulin infusion but not after inhibition of lipolysis by Acipimox.	2005	16179286
[The pharmacokinetics and bioequivalence of acipimox sustained-release tablets after a single and multiple oral administration in healthy dogs].	2005 May	16220793
Effect of a sustained reduction in plasma free fatty acid concentration on intramuscular long-chain fatty Acyl-CoAs and insulin action in type 2 diabetic patients.	2005 Nov	16249438
Effects of GH replacement therapy in adults on serum levels of leptin and ghrelin: the role of lipolysis.	2005 Oct	16189176
Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients.	2005 Oct	16096823
[Effects of atorvastatin and acipimox on the lipid spectrum of blood plasma, endothelial function and a clinical course of unstable angina pectoris].	2006	17078215
Combination therapy with acipimox enhances the effect of growth hormone treatment on linear body growth in the normal and small-for-gestational-age rat.	2006 Dec	16803850
Impact of diabetes mellitus on prediction of clinical outcome after coronary revascularization by 18F-FDG SPECT in patients with ischemic left ventricular dysfunction.	2006 Jan	16391189
Inhibition of lipolysis does not affect insulin sensitivity to glucose uptake in the mourning dove.	2006 Jul	16753324
Potential role of new therapies in modifying cardiovascular risk in overweight patients with metabolic risk factors.	2006 Jun	16931496
Free fatty acids decrease circulating ghrelin concentrations in humans.	2006 May	16645013
Improved triglycerides and insulin sensitivity with 3 months of acipimox in human immunodeficiency virus-infected patients with hypertriglyceridemia.	2006 Nov	16940448
No low-fat diet for the failing heart?	2006 Nov 14	17101867
Intense [18F]FDG tongue uptake in a case of acipimox-related angio-oedema during FDG-PET myocardial viability study.	2007 Aug	17546455
HIV-associated adipose redistribution syndrome (HARS): etiology and pathophysiological mechanisms.	2007 Jun 27	17597538
Reduced plasma free fatty acid availability during exercise: effect on gene expression.	2007 Mar	17186295
Growth hormone-induced insulin resistance is associated with increased intramyocellular triglyceride content but unaltered VLDL-triglyceride kinetics.	2007 Mar	17132823
Dose-response effects of free fatty acids on glucose and lipid metabolism during somatostatin blockade of growth hormone and insulin in humans.	2007 May	17341555
Nicotinic acid receptor subtypes and their ligands.	2007 May	17238156
Human visceral adipose tissue and the plasminogen activator inhibitor type 1.	2007 Nov	17471294
Changes in triglyceride levels over time and risk of type 2 diabetes in young men.	2008 Oct	18591400
Short-term flexibility of myocardial triglycerides and diastolic function in patients with type 2 diabetes mellitus.	2008 Sep	18628354
Endoplasmic reticulum stress: another link between obesity and insulin resistance/inflammation?	2009 Mar	19246600
Diabetes treatment.	2009 Mar	19246581

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage is one 250 mg capsule 2 or 3 times daily to be taken with or after meals. The lower dose is advised in type IV and the higher dose in types IIA and IIB hyperlipoproteinaemias.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

ACIPIMOX

Official Name

English

ACIPIMOX [MI]

Common Name

English

5-METHYLPYRAZINE-2-CARBOXYLIC ACID-4-OXIDE

Systematic Name

English

NSC-759818

Code

English

OLBETAM

Brand Name

English

acipimox [INN]

Common Name

English

ACIPIMOX [MART.]

Common Name

English

Acipimox [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C98151