Nicotinic acid inhibits adipocyte lipolysis via specific nicotinic acid receptors; it lowers low-density lipoprotein (LDL) and Ion Channel Ligand Library price very-LDL cholesterol levels, and it increases high-density lipoprotein (HDL) cholesterol levels [22, 23]. this website Nicotinic acid and NAM have slightly different mechanisms of action. Nicotinic acid alone causes flushing (i.e. prominent cutaneous vasodilatation, particularly in the face) due to its stimulation of prostaglandin D2 and E2 secretion by subcutaneous Langerhans cells via the G-protein-coupled receptor (GPCR) 109A niacin receptor . It was recently reported that both nicotinic
acid and NAM showed efficacy in the treatment of hyperphosphatemia . This review focuses on NAM’s pharmacokinetics, pharmacodynamics, efficacy, and safety. 1.2 Pharmacodynamic Properties The directly absorbed dietary forms of niacin include NAM (the main source, obtained from animal-based foods) and nicotinic acid (obtained from plants). Dietary nicotinic acid is first converted into nicotinamide adenine dinucleotide (NAD) in the intestine and liver and is then cleaved LXH254 chemical structure to release NAM into the bloodstream for uptake by extrahepatic tissues . However, the human body is not completely dependent on direct dietary sources of
niacin, since NAM can also be synthesized from the tryptophan amino acid present in most proteins. Furthermore, NAM is produced by the catabolism of pyridine nucleotides. Nicotinamide’s mechanism of action is not completely understood. In contrast to nicotinic acid, NAM is not a vasodilator, does not bind to GPCR 109A Nintedanib clinical trial and 109B , and thus does not produce flushing. Following filtration in the kidneys, most of the phosphate in the
serum is reabsorbed across the proximal tubule epithelium. Indeed, it has been suggested that the sodium-dependent phosphate cotransport protein 2a (NaPi2a), the cotransporter NaPi2c, and the sodium-dependent phosphate transporter 2 mediate phosphate transport across the apical brush border of proximal tubule cells. In vitro studies have shown that NAM decreases phosphate uptake by inhibiting the cotransporter NaPi2a in the renal proximal tubule and cotransporter NaPi2b in the intestine [28–31] (Fig. 1). Moreover, NAM reduced intestinal phosphate absorption in a rat model of chronic renal failure by inhibiting expression of NaPi2b . The latter transporter’s major role in phosphate regulation in the intestine was recently confirmed by a study of NaPi2b knockout (−/−) mice in which phosphate absorption was half that seen in wild-type animals . Moreover, an in vitro analysis of active phosphate transport in ilial segments from wild-type and NaPi2b knockout mice demonstrated that the transporter is responsible for over 90 % of total active phosphate absorption.