Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “NICOTINIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources
PubMed2006

Crystal structure of nicotinic acid mononucleotide adenylyltransferase from Staphyloccocus aureus: structural basis for NaAD interaction in functional dimer.

Bacterial nicotinic acid mononucleotide adenylyltransferase (NaMNAT; EC 2.7.7.18) encoded by the nadD gene, is essential for cell survival and is thus an attractive target for developing new antibacterial agents. The NaMNAT catalyzes the transfer of an adenylyl group of ATP to nicotinic acid mononucleotide (NaMN) to form nicotinic acid dinucleotide (NaAD). Two independently derived, high-resolution structures of Staphylococcus aureus NaMNAT-NaAD complexes establish the conserved features of the core dinucleotide-binding fold with other adenylyltransferases from bacteria to human despite a limited sequence conservation. The crystal structures reveal that the nicotinate carboxylates of NaAD are recognized by interaction with the main-chain amides of Thr85 and Tyr117, a positive helix dipole and two bridged-water molecules. Unlike other bacterial adenylyltransferases, where a partially conserved histidine residue interacts with the nicotinate ring, the Leu44 side-chain interacts with the nicotinate ring by van der Waals contact. Importantly, the S. aureus NaMNAT represents a distinct adenylyltransferase subfamily identifiable in part by common features of dimerization and substrate recognition in the loop connecting beta5 to beta6 (residues 132-146) and the additional beta6 strand. The unique beta6 strand helps orient the residues in the loop connecting beta5 to beta6 for substrate/product recognition and allows the beta7 strand structural flexibility to make key dimer interface interactions. Taken together, these structural results provide a molecular basis for understanding the coupled activity and recognition specificity for S. aureus NaMNAT and for rational design of selective inhibitors.

Amino Acid Sequence↗
PubMed2005

Flushing out the role of GPR109A (HM74A) in the clinical efficacy of nicotinic acid.

The recent discovery of the G(i) protein-coupled receptor GPR109A (HM74A in humans; PUMA-G in mice) as a receptor for nicotinic acid has provided the opportunity to gain greater understanding of the underlying biology contributing to the clinical efficacy (increases in HDL, decreases in VLDL, LDL, and triglycerides) and the characteristic side-effect profile of nicotinic acid. GPR109A has been proven to be the molecular target for the actions of nicotinic acid on adipose tissue, and in this issue of the JCI, Benyó et al. have confirmed the involvement of GPR109A in the nicotinic acid-induced flushing response, a common side effect. The involvement of GPR109A in both the desirable and undesirable clinical actions of nicotinic acid raises interesting questions regarding the function of this receptor.

Adipocytes↗
PubMed1977

A comparison of cholestyramine and nicotinic acid in the treatment of familial type II hyperlipoproteinaemia.

1 The effects of cholestyramine and nicotinic acid on plasma lipid concentration have been compared in patients with type IIa hyperlipoproteinaemia. 2 During a 3-month period, cholestyramine resulted in a mean decrease in cholesterol levels of 26%. Triglyceride levels rose in eight of the ten patients during treatment with this drug but in the majority of patients remained within the normal range. 3 During nicotinic acid therapy, cholesterol fell by a mean of 21% and triglyceride by a mean of 23%. 4 The slow release preparation of nicotinic acid used was acceptable to the majority of the patients studied and the results therefore suggest that this drug may be a useful alternative to the more widely used agent, cholestyramine.

Adolescent↗
PubMed1981

Colestipol plus nicotinic acid in treatment of heterozygous familial hypercholesterolaemia.

Thriteen patients with heterozygous familial hypercholesterolaemia (FH) were sequentially treated with: a low-cholesterol, fat-restricted diet; diet and colestipol; and diet and colestipol and nicotinic acid. Concentrations of plasma cholesterol decreased from 415 +/- 69 mg/dl on diet alone to 327 +/- 54 mg/dl on colestipol and fell to 246 +/- 49 mg/dl on the combined drug regimen. Plasma concentrations of LDL cholesterol declined 24% on colestipol; the subsequent addition of nicotinic acid resulted in a further 31% fall so that values on the combined drug regimen were 47% below those seen on diet alone. HDL cholesterol levels were similar on both the diet (40 mg/dl) and colestipol (43 mg/dl) treatment periods but increased to 53 mg/dl on the combined drug regimen. Treatment resulted in significant decreases in the LDL:HDL ratio which fell from 8.4 on diet to 3.3 on the colestipol plus nicotinic acid regimen. In most patients with heterozygous FH, combined use of a bile acid sequestrant and nicotinic acid affords the opportunity to maintain a normal lipid profile. Prolonged use of this regimen may reduce the incidence of premature coronary atherosclerosis which naturally occurs in these patients.

Adult↗
PubMed2001

Effect of drug lipophilicity on in vitro release rate from oil vehicles using nicotinic acid esters as model prodrug derivatives.

The rate constants for transfer of a homologous series of nicotinic acid esters from oil vehicles to aqueous buffer phases were determined using a rotating dialysis cell. The chemical stability of butyl nicotinate has been investigated at 60 degrees C over pH range 0.5--10. Maximum stability occurs at pH 4--5 and an inflection point was seen around the pK(a). For the nicotinic acid esters, a linear correlation was established between the first-order rate constant related to attainment of equilibrium, k(obs) and the apparent partition coefficient, P(app): log k(obs)=-0.83log P(app)+0.26 (k(obs) in h(-1), n=9). For hexyl nicotinate with a true partition coefficient of 4 it was possible to determine k(obs) by decreasing pH in the aqueous release medium to 2.05. Thus, under the latter experimental conditions estimation of the relative release rates for the esters were performed. The ratio between the specific rate constant k(ow), related to the transport from oil vehicle to aqueous phase, for ethyl and hexyl nicotinate was 139. The hydrophobic substituent constant for a methylene group, pi(CH(2)), was determined for nicotinic acid esters in different oil/buffer partitioning systems to 0.54--0.58. Addition of hydroxypropyl-beta-cyclodextrin to the aqueous release medium did not enhance the transport rate of the esters from the oil phase.

Chemistry, Pharmaceutical↗
PubMed2003

Chemical stability of esters of nicotinic acid intended for pulmonary administration by liquid ventilation.

PURPOSE: It has been suggested that fluorocarbon liquid may be a unique vehicle for the delivery of drugs directly to the acutely injured lung. A prodrug approach was used as a means of enhancing the solubility of a model drug (nicotinic acid) in the fluorocarbon. The solubility, the chemical stability of the putative prodrugs, and the sensitivity to enzymatic hydrolysis was investigated. METHODS: The solubility of each nicotinic acid ester was determined in buffer as a function of pH and in perflubron. The octanol/buffer partition coefficient was determined at pH 7.4. The chemical stability of the putative prodrugs was determined as a function of pH, temperature, buffer content, and ionic strength. In addition, sensitivity of the esters to enzymatic degradation was evaluated. RESULTS: Compared with nicotinic acid, the solubility in perflubron of the esters was significantly enhanced. In aqueous buffers, the esters exhibited pseudo-first order degradation kinetics, with both acid and base catalyzed loss. Studies of the fluorobutyl ester indicate quantitative loss of the putative prodrug and release of the parent nicotinic acid. Porcine esterase accelerated the loss of fluorobutyl ester by a factor of over 200 compared with chemical hydrolysis at pH 7.4. CONCLUSIONS: The properties of the fluorinated esters suggest that they may be suitable candidates for further testing as possible prodrugs of nicotinic acid based upon higher solubility in perflubron, rapid release of the parent drug after simple hydrolysis, and sensitivity to the presence of a model esterase enzyme.

Algorithms↗
PubMed1977

Spectrophotometric assay of nicotinic acid in blood. Assessment of its daily profile in humans.

A sensitive, simple, and specific spectrophotometric method is developed for estimating nicotinic acid in blood. The method depends upon reducing nicotinic acid by Zn/HCl to piperidine-3-carboxylic acid. The latter is complexed with CS2 and ammoniacal CuSO4 to form the yellow Cu-dithiocarbamate complex. The color is measured at 445 nm, obeys Beer's law (20--900 microgram/ml), and remains stable for more than 4 h. Efficiency of recoveries from standards and blood samples was tested and proved satisfactory at different levels of concentrations. The method shows good recovery (99.66%) and reasonable standard deviation (+/- 0.29%) in comparison with the cyanogen bromide method (98.3% and +/- 0.73%, respectively). The results obtained show a natural gradual decline in blood nicotinic acid level during the course of the day.

Female↗
PubMed1988

Effect of nicotinic acid administration on serum levels of bilirubin and iron in patients with porphyria cutanea tarda.

Nicotinic acid (NA) administration in Gilbert's syndrome (GS) patients promotes an increment of bilirubin and of total iron serum levels, dependent on a defective hepatic bilitranslocase function and on a haemolytic effect of NA. In porphyria cutanea tarda (PCT): (1) the effect of nicotinic acid on bilirubinaemia is superimposable to that in controls; (2) a well documented disturbance of iron metabolism occurs; (3) but relationship between bilirubin and iron under NA load has never been investigated. The administration of 5.9 mumol/kg body weight of NA to 12 PCT patients, 10 GS subjects and nine healthy volunteers of comparable age resulted in: (1) normal behaviour of bilirubin parameters in PCT but higher bilirubinaemic values in GS subjects; (2) normal values of serum iron in GS subjects, but higher baseline values and lower sideraemic effect of nicotinic acid in PCT patients; (3) a normal NA half-life in PCT and enhanced in GS subjects. These findings confirm a defective bilirubin uptake and excretion by the liver of GS subjects with a normal iron metabolism. On the contrary, in our PCT patients a normal clearance of bilirubin occurs, but a complex disturbance of iron metabolism is well evident in baseline conditions as well as after NA administration. The latter being probably the consequence of an enhanced excretion of iron extraproduced by the haemolytic effect of NA.

Adult↗
PubMed1996

Therapy of primary biliary cirrhosis with p-tolylmethylcarbinol nicotinic acid ester in combination with alpha-naphthylacetic acid.

OBJECTIVE: To assess the effect of choleretic treatment with p tolylmethylcarbinol nicotinic acid ester and alpha-naphthylacetic acid (Galle-Donau) on laboratory parameters of cholestasis, lipids, immunologic activity and on clinical signs in primary biliary cirrhosis patients. DESIGN: Prospective, non-randomized case control study; retrospective evaluation of pre-treatment period, evaluation of six months of treatment, open study after six month of treatment with evaluation of patients further treated and patients who discontinued treatment. PATIENTS AND METHODS: Twelve consecutive patients with proven primary biliary cirrhosis, all female. Patients were to take six to nine capsules of Galle-Donau, containing 37.5 mg p-tolymethylcarbinol nicotinic acid ester and 75 mg alpha-naphthylacetic acid (5 mg per kg of body weight and 10 mg), daily in three doses, together with meals. Six patients discontinued treatment with Galle-Donau after six months and were followed up further. RESULTS: After six months of Galle-Donau treatment the average alkaline phosphatase level dropped from 670.8 IU/ml to 577.1 IU/ml; the levels of total bilirubin (1.46 vs. 1.15 mg/100 ml) and unconjugated bilirubin (0.82 vs. 0.63 mg/100 ml) also decreased under therapy. This drop was not significant, while the decrease in triglycerides (149.2 vs. 103.1 mg/100 ml) reached statistical significance. During further treatment for up to two years patients showed no significant change in triglycerides, cholesterol or alkaline phosphatase. y-Glutamyl transpeptidase was not changed by treatment. Discontinuance of treatment resulted in significant increases in alkaline phosphatase and y-glutamyl transpeptidase, as well as in bilirubin levels. Triglyceride values also rose significantly when treatment was stopped, while the increase in cholesterol did not reach statistical significance. No influence of Galle-Donau treatment was found on IgM level. Pruritus (five patients) and Sicca symptoms (six patients) resolved within the treatment period in all but one patient (Sicca symptoms) who did not take the medication regularly. In the group of patients who discontinued therapy pruritus returned in both patients who had complained of it before therapy. Sicca symptoms returned in one out of three patients. CONCLUSION: Treatment with p-tolylmethylcarbinol nicotinic acid ester and alpha-naphthylacetic acid leads to relief of symptoms and ameliorates biochemical parameters of cholestasis may, therefore, be of value for PBC therapy.

Adult↗
PubMed2005

Nicotinic acid in the management of dyslipidaemia associated with diabetes and metabolic syndrome: a position paper developed by a European Consensus Panel.

Individuals with type 2 diabetes and metabolic syndrome are at markedly increased risk of cardiovascular morbidity and mortality. The increasing prevalence of both conditions poses a major challenge for clinicians in the 21st century. Both diabetes and metabolic syndrome are associated with a clustering of cardiovascular risk factors. In particular, dyslipidaemia characterised by low plasma levels of high-density lipoprotein cholesterol (HDL-C), elevated triglycerides and an increase in small, dense low-density lipoprotein (LDL) particles (the lipid triad), has been established as the most important modifiable risk factor for coronary heart disease (CHD). Current treatment guidelines recognise the increased CHD risk associated with diabetes and metabolic syndrome and focus on LDL-C lowering with statin treatment, in addition to dietary and lifestyle modification, as the primary lipid-modifying therapy. However, while there is no doubt that statin therapy significantly reduces CHD risk in these patients, their residual absolute risk remains higher than in individuals without diabetes or metabolic syndrome. Thus, there is a clear need to target other aspects of lipoprotein metabolism, notably low HDL-C and hypertriglyceridaemia, to further reduce CHD risk. Combining statin therapy (targeting LDL-C) with interventions that also modify low HDL-C and elevated triglycerides could be a useful strategy to optimise CHD risk reduction. Cautious combination of a fibrate or nicotinic acid with a statin is useful for the management of combined dyslipidaemia. Nicotinic acid is the more potent agent for raising HDL-C (by up to 29% at clinically recommended doses). It also substantially reduces triglycerides and LDL-C, and promotes a shift from small, dense LDL to larger, more buoyant LDL particles. Preliminary clinical data suggest that combining nicotinic acid with a statin will produce a greater reduction in cardiovascular risk in patients with diabetes and metabolic syndrome than statin monotherapy alone. Nicotinic acid is also safe for use in patients with diabetes, with no evidence of clinically relevant deterioration in glycaemic control at recommended doses (< or = 2 g/day). On review of the available evidence, this European Consensus Panel recommends the combination of nicotinic acid and a statin, together with lifestyle modification, as a useful strategy to lower CHD risk in patients with diabetes and metabolic syndrome. Prolonged-release nicotinic acid with improved tolerability compared with previous formulations may have obvious advantages for use in this setting.

Cardiovascular Diseases↗
PubMed1990

Comparison of effects of nicotinic acid or tryptophan on tryptophan 2,3-dioxygenase in acute and chronic studies.

Tryptophan is one of the strongest activators of tryptophan 2,3-dioxygenase, the rate-limiting enzyme in the pathway which degrades tryptophan. One of the metabolites thus formed is nicotinic acid, widely administered as a drug--often at high doses--and a vitamin. This study determined whether nicotinic acid also has a potency to activate tryptophan 2,3-dioxygenase and, if so, by what mechanism, whether changes in plasma tryptophan result, and if such activation is permanent. The results showed that nicotinic acid activated the enzyme almost as strongly as tryptophan. The results confirmed the activation to be of the "substrate" type, i.e., at least partly due to increased tryptophan concentrations in the liver. In repeated nicotinic acid administration plasma tryptophan levels did not diminish, despite the high activation of tryptophan 2,3-dioxygenase (high flux of tryptophan through the kynurenine pathway). However, the activation disappeared after 11 days of treatment. The powerful and sustained activation of tryptophan 2,3-dioxygenase by nicotinic acid may at least partly explain some of its side effects, such as glucose intolerance. However, mental disturbance as a side effect of diminished brain levels of tryptophan is not supported by these findings.

Animals↗
PubMed1996

Acute dose-dependent disposition studies of nicotinic acid in rats.

The pharmacokinetics of nicotinic acid (NiAc) and nicotinuric acid (NiUAc), the major metabolite of NiAc, and the dose dependency of these pharmacokinetics were determined in rats. Intravenous injections of 2, 5, 15, and 45 mg/kg of NiAc and 5 and 15 mg/kg of NiUAc were administered, and plasma and urine samples were assayed for NiAc and NiUAc by HPLC. The plasma concentration-time profiles of NiAc showed a typical characteristic of capacity-limited elimination after higher doses. When the NiAc dose was elevated, the total plasma clearance of NiAc decreased dramatically, and the normalized area under the plasma concentration-curve increased markedly. There was no change in the volume of distribution at steady state. After the administration of NiUAc, however, the pharmacokinetics of NiUAc were linear, at least up to a dose of 15 mg/kg. With increasing doses of NiAc, the ratio for NiUAc to unchanged drug excreted in urine decreased markedly from 4.54 +/- 0.93 at 2 mg/kg to 0.37 +/- 0.12 at 45 mg/kg while the renal clearance of NiAc remained constant. An in vitro study of the plasma protein binding of NiAc showed no saturability, with a 40 to 50% bound fraction, when total NiAc concentrations were 1 to 130 micrograms/ml. Plasma NiAc profiles after the iv administration of NiAc were adequately described by the two-compartment model including the "pooled" Michaelis-Menten elimination process. The present results suggest that the nonlinear disposition of NiAc can be attributed in part to the saturation of glycine conjugation, and also, probably to amidation.

Animals↗
PubMed1987

The role of copper(I)-nicotinic acid complex on kojic acid biosynthesis by Aspergillus flavus.

Addition of cooper-monovalent-nicotinic acid complex to a synthetic medium specific for kojic acid production by Aspergillus flavus enhanced the production by about 47%. The substance is proposed to act via a biochemical utilization of the copper(I)-B3 complex in a manner similar to that of the naturally utilized nicotinic acid. NAD and NADP like carriers with higher reactivity have been predicted. According to this prediction the biosynthetic route of kojic acid has been interpreted on the basis of a model proposed by Bajpai et al. (1981). In this model the enzymes participating are dependent on NAD and NADP (glucose dehydrogenase and gluconate dehydrogenase) as well as on other reduction processes.

Aspergillus flavus↗
PubMedDate not supplied

[Uptake of 14C-nicotinic acid by membrane structures of rat tissue in alloxan diabetes with insulin administration].

The uptake of nicotinic acid by erythrocytes, hepatocytes and inverted small intestine sacs of rats with alloxane diabetes was studied as affected by insulin. It is established that a disturbance of the pancreas endocrine function caused by the administration of alloxane to rats inhibits the accumulation of [14C]nicotinic acid in all the studied structures. Insulin administered to rats with alloxane diabetes stimulates the acid uptake by erythrocytes and hepatocytes, but has no effect on accumulation of the vitamin in tissues and serous fluid of inverted empty intestine sacs. An assumption is advanced that under alloxane diabetes the membrane transport of nicotinic acid is disturbed and it may be partially normalized by the insulin administration. The efficiency of the hormone influence on the vitamin uptake by the structures under study changes essentially against a background of the actinomycin D and cycloheximide action.

Animals↗
PubMed1975

Insulin, prostaglandin E1, PHENYLISOPROPYLADENOSINE AND NICOTINIC ACID AS REGULATORS OF FAT CELL METABOLISM.

Insulin-stimulated glucose oxidation was enhanced by the addition of N6 (phenylisopropyl)adenosine (PIA), prostaglandin E1 (PGE1) or nicotinic acid during a 1-h incubation of small amounts 5-8 mg/ml) of rat fat cells. Basal lipolysis was appreciable if low numbers of fat cells were incubated per ml. Insulin inhibited basal lipolysis at 20 to 50 mugU/ml and abolished lipolysis of 100 mugU/ml was present over a l-h period. However PIA, PGE1 or nicotinic acid potentiated glucose oxidation due to the 100 mugU/ml dose of insulin indicating that these agents are not increasing glucose oxidation solely as a result of an inhibition of lipolysis. PIA, PGE1 and nicotinic acid acted synergistically with insulin in stimulating glucose oxidation and inhibiting lipolysis in the presence of norepinephrine. Insulin was unable to decrease basal cyclic AMP accumulation or the increase in cyclic AMP seen with norepinephrine and theophylline after various time periods (2 to 60 min) but PIA, PGE1 and nicotinic acid were able to inhibit cyclic AMP accumulation at all times tested.

Adipose Tissue↗
PubMed1980

Effect of nicotinic acid on the concentration of cerebroside in rat brain.

The effect of nicotinic acid on the changes of rat brain cerebroside levels has been studied during brain development. There is a gradual increase in the concentration of cerebroside from 12 days of age to adult level at approximately 47 days of age. However, the concentration of cerebroside was significantly lower in brain of rat fed the nicotinic acid-deficient diet. Therefore, nicotinic acid may play an important role in cerebroside synthesis in brain of developing rat.

Age Factors↗
PubMed1998

Simultaneous determination of nicotinic acid and its metabolites in rat urine by micellar electrokinetic chromatography with photodiode array detection.

Nicotinic acid, nicotinamide and their possible metabolites were successfully separated within 17 min by micellar electrokinetic chromatography using 50 mM borate buffer (pH 9.0) containing 150 mM sodium dodecyl sulfate as the running buffer. Calibration curves for all compounds showed good linearity in a range of 5 microg/ml and 250 microg/ml with good correlation. The present method did not require any clean-up procedures and made it possible to determine all metabolites without interference on a photodiode array detector. Urine samples collected from Wistar male rats were analyzed after high-dose oral or intravenous administration of nicotinic acid or nicotinamide. Metabolic pathways of nicotinic acid in male Wistar rats are also discussed.

Animals↗