Disease relevance of nicotinic acid

• Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease [1].
• Niacin Reduces Paraquat Toxicity in Rats [2].
• Niacin-treated rats showed delayed and reduced dyspnea [2].
• Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus [3].
• The IR niacin is preferred for the management of hypercholesterolemia but can also cause significant adverse effects and should be given only to patients who can be carefully monitored by experienced health professionals [4].

Psychiatry related information on nicotinic acid

• The dyslipidaemic profile of diabetes greatly contributes to the increased cardiovascular risk associated with the disorder, and evidence from many intervention trials using statins, fibrates, nicotinic acid or a nicotinic acid-statin combination, indicates the substantial cardiovascular risk reduction to be gained from lipid modification [5].
• Niacin should be avoided in patients with hepatic dysfunction or a history of liver disease, patients with diabetes mellitus, and patients who abuse alcohol [6].
• In the present study, niacin-induced vasodilation was estimated quantitatively in schizophrenic and comparison bipolar affective disorder and healthy subjects using thermocouple sensors to measure the change in skin temperature relative to core body and ambient room temperature [7].
• Twelve (42.9%) of 28 schizophrenic subjects did not vasodilate in response to a 200-mg niacin challenge dose, whereas only 1 of 18 (6%) bipolar disorder subjects and none of 28 controls showed impaired response (Fisher's Exact Test, p < .0001) [7].
• These have advantages over cholestyramine and nicotinic acid in terms of better patient compliance [8].

High impact information on nicotinic acid

• For the bile acid sequestrants, niacin, and gemfibrozil, the risks of discontinuation were substantially higher in the HMOs than in randomized clinical trials, in which the summary estimates of this risk were 31 percent, 4 percent, and 15 percent, respectively, for trials of one year or longer [9].
• Binding of nicotinic acid to PUMA-G or HM74 results in a G(i)-mediated decrease in cAMP levels [10].
• A G-protein-coupled receptor for nicotinic acid has been proposed in adipocytes [10].
• This anti-lipolytic effect of nicotinic acid involves the inhibition of cyclic adenosine monophosphate (cAMP) accumulation in adipose tissue through a G(i)-protein-mediated inhibition of adenylyl cyclase [10].
• In mice lacking PUMA-G, the nicotinic acid-induced decrease in free fatty acid (FFA) and triglyceride plasma levels was abrogated, indicating that PUMA-G mediates the anti-lipolytic and lipid-lowering effects of nicotinic acid in vivo [10].

Chemical compound and disease context of nicotinic acid

• Effect of the antilipolytic nicotinic acid analogue acipimox on whole-body and skeletal muscle glucose metabolism in patients with non-insulin-dependent diabetes mellitus [11].
• These results support the hypothesis that a reduced availability of the essential amino acid L-tryptophan may limit the synthesis of albumin and nicotinic acid in patients with the carcinoid syndrome who become anoretic [12].
• Lovastatin, nicotinic acid, and rhabdomyolysis [13].
• CONCLUSIONS: Colestipol, lovastatin, and niacin are mutually complementary in treating hypercholesterolemia [14].
• We report an extensive characterization of the Na(+)/monocarboxylate transporter (SMCT), a plasma membrane protein that mediates active transport of monocarboxylates such as propionate and nicotinate, and we show that SMCT may play a role in colorectal cancer diagnosis [15].

Biological context of nicotinic acid

• Nicotinic acid reduction of plasma volume loss after thermal trauma [16].
• In the Coronary Drug Project, individuals with diabetes or insulin resistance derived as much as 70% cardiovascular risk reduction from the HDL-C elevations achieved with nicotinic acid therapy [5].
• Nicotinic acid and skin temperature [17].
• Letter: Nicotinic acid and myocardial action potential [18].
• Pharmacoepidemiology of niacin [19].

Anatomical context of nicotinic acid

• The mouse orthologue of GPR109A, PUMA-G, is highly expressed in macrophages and other immune cells, and transplantation of wild-type bone marrow into irradiated PUMA-G-deficient mice restored the nicotinic acid-induced flushing response [20].
• Prevention and reversal of cholera enterotoxin effects in rabbit jejunum by nicotinic acid [21].
• A randomised controlled clinical trial was conducted to investigate the ability of nicotinic acid to reduce intestinal secretion in patients with severe cholera [22].
• Furthermore, rsc4 mutants displayed defects in the activation of genes involved in nicotinic acid biosynthesis, cell wall integrity, and other pathways [23].
• With all three end points, the benefit of colestipol/niacin treatment on coronary artery atherosclerosis has been reported [24].

Associations of nicotinic acid with other chemical compounds

• Glucose levels were modestly increased by niacin (8.7 and 6.3 mg/dL [0.4 and 0.3 mmol/L]; P =.04 and P<.001) in participants with and without diabetes, respectively [25].
• METHODS AND RESULTS: The Cholesterol Lowering Atherosclerosis Study randomized 162 nonsmoking, 40- to 59-year-old men with previous coronary artery bypass graft surgery to colestipol/niacin plus diet or placebo plus diet [24].
• beta-Adrenergic agonists such as isoproterenol stimulate hamster adipocyte adenylate cyclase by a GTP-dependent process, whereas prostaglandin E1, alpha-adrenergic agonists, and nicotinic acid inhibit the enzyme by a process also dependent on GTP and amplified by sodium ions [26].
• Five classes of lipid-lowering drugs are approved by the Food and Drug Administration (FDA) for use in the United States: nicotinic acid, bile acid sequestrants, fibric acid derivatives, reductase inhibitors, and probucol [27].
• Normalization of plasma lipoprotein concentrations in patients with type II hyperlipoproteinemia by combined use of neomycin and niacin [28].

Gene context of nicotinic acid

• Pnc1 is a nicotinamidase that converts NAM to nicotinic acid [29].
• Together with data from molecular modeling studies, our data suggest that the ligand binding pocket for nicotinic acid of GPR109A is distinct from that of most other group A receptors [30].
• To investigate the structural determinants of GPR109A ligand binding, we performed site-directed mutagenesis of putative ligand binding residues combined with generation of chimeric receptors consisting of GPR109A and its close relative GPR109B, which does not bind nicotinic acid [30].
• Effects of nicotinic acid therapy on plasma lipoproteins and very low density lipoprotein apoprotein C subspecies in hyperlipoproteinemia [31].
• Gel isoelectric focusing of VLDL before and after nicotinic acid in types IIb and IV hyperlipidemia produced a significant increase in the VLDL ApoC-II component with simultaneous decreases in the total VLDL ApoC-III subspecies [31].

Analytical, diagnostic and therapeutic context of nicotinic acid

• Insulin resistance was induced by a 20-d continuous intravenous infusion of nicotinic acid (NA) [32].
• These data, along with history and physical examination findings, suggest that niacin deficiency is not responsible for the rash, which is more characteristic of an acquired ichthyosis [33].
• A large portion of the radioactive material from P. putida was found to be nicotinic acid by 1H NMR spectroscopy, gas-liquid chromatography of its methyl ester, and co-crystallization with authentic reference compounds both as the acid and as the hydrazide [34].
• Nicotinic acid, pharmacological doses of sex hormones and anabolic steroids, as well as LDL apheresis may provide sufficient lowering of lipoprotein (a) for the evaluation of clinical response [35].
• X-ray crystallography has shown that the heme cavity can easily accommodate ligands the size of nicotinate, and analysis of extended x-ray absorption fine structure data has shown that the Fe atom is in the mean plane of the heme in the leghemoglobin-CO complex [36].

References