Action Of Nicotinic Acid Research Articles

Nicotinic acid as a lipid-modifying drug – A review

Nicotinic acid has complex effects on lipoprotein metabolism; it increases HDL cholesterol, decreases triglycerides and LDL cholesterol. It also reduces lipoprotein(a) levels by about 25% and exerts certain effects that may be antiatherogenic. Studies performed in the pre-statin era demonstrated a good effectiveness of nicotinic acid on the development of atherosclerotic lesions and on the morbidity and mortality due to cardiovascular diseases. Because of its HDL cholesterol raising properties, nicotinic acid appears to be an ideal companion to statins since low HDL cholesterol concentration has been shown to negatively influence statin-treated patients even when ideal LDL cholesterol concentrations have been reached. In the AIM-HIGH study nicotinic acid did not lead to an improvement in the cardiovascular event rate compared to placebo; however this study has been criticized because of several drawbacks. The results of a large study testing the effect of nicotinic acid in high-risk statin-treated patients are expected to be published in 2013. At present, nicotinic acid can be administered in addition to a statin to patients with a combined hyperlipidemia when the target value of LDL cholesterol has not been reached, and alone to patients suffering from a statin intolerance. An elevation of lipoprotein(a) is not officially recognized as an indication to start a therapy with nicotinic acid. The combination of modified-release nicotinic acid with laropiprant is much better tolerated than previous formulations. New drugs which act on the receptor involved in the action of nicotinic acid are in development.

Nicotinic acid: an old drug with a promising future

Nicotinic acid has been used for decades to treat dyslipidaemic states. In particular its ability to raise the plasma HDL cholesterol concentration has led to an increased interest in its pharmacological potential. The clinical use of nicotinic acid is somewhat limited due to several harmless but unpleasant side effects, most notably a cutaneous flushing phenomenon. With the recent discovery of a nicotinic acid receptor, it has become possible to better understand the mechanisms underlying the metabolic and vascular effects of nicotinic acid. Based on these new insights into the action of nicotinic acid, novel strategies are currently under development to maximize the pharmacological potential of this drug. The generation of both flush-reducing co-medications of nicotinic acid and novel drugs targeting the nicotinic acid receptor will provide future therapeutic options for the treatment of dyslipidaemic disorders.

Photosensitization and photoprotection properties of nicotinic acid derivatives

The photosensitizing action of nicotinic acid, nicotinamide, and nicotinehydroxymethylamide on the photooxidation of glycyltryptophan (Gly-Trp) in an aqueous solution using UV light (240–410 nm) was found. The photooxidation was monitored by measuring chemiluminescence (CL) resulting from the decay of one of the oxidation products, dioxethane. The photosensitizing action decreases in the following sequence: nicotinamide > nicotine-hydroxymethylamide > nicotinic acid. The addition of benzoquinone (0.01 mmol L−1) results in a substantial decrease in the yield of sensitized CL, which indicates that the superoxide radical anion participates in the photooxidation.

THE EFFECT OF NICOTINIC ACID ON THE DEPRESSANT ACTION OF ETHANOL AND PENTOBARBITAL

The effect of nicotinic acid (NA) on sleeping time induced by a single dose of ethanol or pentobarbital was studied in rats. It was found that sleeping time was markedly reduced by NA in a dose-dependent manner. The effect was observed when NA was administered 10 min before or after ethanol or pentobarbital, but not when given 60 min in advance. NA did not affect the rate of ethanol elimination measured up to 5 hr after ethanol administration. Rats pretreated with NA 60 min before ethanol slept longer than controls. This latter effect was not observed with pentobarbital. These observations, together with the known lack of effect of high liver NAD+ levels on ethanol metabolism and the rather stable NAD+ concentration in brain cells, suggest that the effect of NA on sleeping time is not mediated by an increase in ethanol metabolism in liver or by NAD+ or NAD+-dependent reactions in brain. Our results are consistent with a direct action of NA, or some rapidly formed derivative, on a structure or process associated with brain cell functions or membranes.

Investigation of the role of cyclic AMP and prostaglandin E2 in the mechanism of the inhibitory action of nicotinic acid on platelet aggregation

Investigation of the role of cyclic AMP and prostaglandin E2 in the mechanism of the inhibitory action of nicotinic acid on platelet aggregation

Role of artificial ventilation of the lungs in mechanisms of development of generalized electrical activity of limbic origin after resuscitation

In frogs (Rana temporaria) injection of L-kynurenine, quinolinic, nicotinic and picolinic acids (10 microgram) into brain ventricles potentiated the stimulant ad convulsant effects of a subthreshold dose of strychnine. Xanthurenic and anthranilic acids were ineffective. At a dose of 100 micrograms picolinic acid produced seizures in 25% of animals, quinolinic acid and L-kynurenine motor excitement in all animals, and the action of nicotinic acid was shown by severe muscle hypotonus. The doses lower than 100 g proved inactive.

Effect of nicotinic acid on gastric secretion of acid in human subjects and in dogs.

The effect of nicotinic acid on gastric secretion was studied in 19 fasting patients who had coronary heart disease and hyperlipoproteinemia. Among 10 patients with basal secretion of acid, 9 had increased acid output following oral administration of 0.5 g of nicotinic acid — the increase ranged from 13 to 232 per cent. Also in Pavlov pouch dogs, i.v. infusion of nicotinic acid gave rise to a significant increase in gastric acid output. The mechanism behind gastric stimulatory action of nicotinic acid is unknown.

EFFECT OF NICOTINIC ACID ON STEROL BIOSYNTHESIS IN SACCHAROMYCES CEREVISIAE.

IN 1955, Altschul et al. reported1 that large doses of nicotinic acid, but not of its amide, decreased serum cholesterol-levels in man and rabbit. This finding has been confirmed by many workers2. Despite several investigations of mechanisms, however, the locus of the nicotinic acid effect remains unknown3,4. We wish to report an effect of high concentrations of nicotinic acid on sterol biosynthesis in yeast. This effect may account for the hypocholesteremic action of nicotinic acid.

Production of Ketosis in Alloxan Diabetic Rats with Nicotinic Acid

SummaryA series of 20 rats of the Long-Evans strain which had severe alloxan diabetes for a preliminary period of 2 to 4 months, was given a diet with excess nicotinic acid. The diet was adequate but contained 1 g niacin/kg. The most outstanding effect of this diet was the production of ketonuria in 16 of the 20 animals, although the degree of ketonuria and the response pattern was variable. Supplementary choline did not inhibit ketosis. The action of nicotinic acid in altering fat metabolism is discussed.

Action of Nicotinic Acid on Coagulation of the Blood

SummaryNicotinic acid has no coagulant effect when tested in vitro with heparinized recalcified plasma. Its coagulant action is comparable to that of distilled water when tested in vitro with heparinized whole blood. Nicotinic acid is an active hemolytic agent and its coagulant effect is apparently due to the release of thromboplastin from the disrupted elements of the blood. Compounds of nicotinic acid which do not produce significant hemolysis have no appreciable coagulative potency.

Inhibition by Sulfapyridine of the Curative Action of Nicotinic Acid in Dogs

SummaryWhen dogs were placed on a diet deficient in nicotinic acid, the addition of nicotinic acid corrected the deficiency, while the addition of nicotinic acid and sulfapyridine failed to do so. When raw liver and sulfapyridine were added to the diet, the deficiency disappeared. It seems possible, but not proven, that sulfapyridine inhibits the action of nicotinic acid but not of preformed coenzymes.