Physical and Chemical Properties
White or almost white crystalline powder, odorless, bitter taste. It is soluble in methanol, ethanol, chloroform, dissolved in acetone, ethyl ether, almost insoluble in water. Valid form used in clinic is H-type, mp 137~141 ℃. [Α] D-37.5 °, the maximum UV absorption wavelength in methanol is 252,257,263nm.
The above information is edited by the chemicalbook of Tian Ye.
Nateglinide and mitiglinide, repaglinide are three commonly used non-sulfonylurea oral hypoglycemic agents for insulin secretion,it is successfully developed for the first time by the Japanese company Ajomoto , its chemical structure belongs to carbamoylmethyl-benzoic acid (CMBA), it belongs to D-phenylalanine derivatives, it is a new generation of antidiabetic drugs having amino acid structure ,it is an amino acid derivative prompting insulin secretion, it is also currently the only non-sulfonylureas insulinotropic agent having amino acid structure. The mechanism is mainly through binding the pancreatic β cell sulfonylurea receptor, blocking islet cell ATP-sensitive potassium channels, leading to membrane depolarization, causing the calcium channe lopen to promote insulin secretion. This product is a new type of meal blood glucose regulator, which can effectively control the postprandial blood glucose levels, with rapid onset, short duration of action, low incidence of cardiovascular side effects and hypoglycemia and other characteristics.
Oral bioavailability is 72%, after 15min it can produce insulin secretion effect, Tmax is 0.5~0.9 h, 0.2 h insulin levels achieve peak ,after 1.5 h it is similar to placebo. The plasma protein binding rate is 99%. After reaching plasmapeak , plasma concentrations decline rapidly.T1/2 of oral administration of 120 mg and intravenous injection 60 mg of is 1.5 to 1.7 hours, and the plasma clearance is 7.4 hours. It is metabolized in the liver by isoenzyme CYP2C9 and CYP3A4 way. The main metabolites are products after isomeric oxidation,it can be hydroxyl, diastereomers, isopropyl isomer or unsaturated aliphatic isomers.The main metabolites in plasma and urine are metabolites after the hydroxylation of isopropyl methine family (me-thine carbon) . About 2/3 nateglinide is excreted from the fecal , and the rest is excreted in the urine. Such excretion way is beneficial to elderly Ⅱ diabetes mellitus with renal dysfunction. nateglinide eliminate T1/2 is 1.4 h, because nateglinide T1/2 is short, there is no report yet about the drug accumulation in the body . Long-term use of nateglinide does not produce drug-induced hypoglycemia caused by drug accumulation .It is used for the treatment of diet therapy, exercise therapy and mild to moderate non-insulin dependent (Ⅱ type) diabetes which taking α-glucosidase inhibitor can not control. The results show that: nateglinide can be used more physiologically for meal glucose control, there is less opportunity for contact with insulin and hypoglycemia which allows patients to flexibly plan scheduling mealtimes, which means there is medication while eating, not eating no medication.
It is used for the treatment of diabetes
Nateglinide is a N-acylated D-phenylalanine marketed in
Japan as novel orally active insulinotropic agent for the treatment of type-2
diabetes mellitus. It belongs to the class of nonsulfonylureas and shows some
structural similarity to repaglinide, the only other representative in this family. In
single pancreatic beta-cells isolated from rats, Nateglinide was found to
specifically block the ATP-sensitive K+ channel resulting in an increase in
intracellular calcium concentration. This primary action would underlie the
mechanism by which Nateglinide markedly stimulates or potentiates, depending
on glucose concentrations, insulin secretion from pancreatic beta-cells. Clinical
studies demonstrated a good safety profile with a low potential for
hypoglycemia. The pharmacokinetic profile was consistent with the changes of
the blood glucose and plasma insulin level. Interestingly, Nateglinide exerts a
rapid onset and short duration of action due to a rapid absorption and clearance.
Unlike other similar agents, Nateglinide suppresses postprandial glucose
elevations.
An amino-acid derivative that stimulates insulin secretion. Used as an antidiabetic.
antidiabetic KATP channel blocker
ChEBI: An N-acyl-D-phenylalanine resulting from the formal condensation of the amino group of D-phenylalanine with the carboxy group of trans-4-isopropylcyclohexanecarboxylic acid. An orally-ad
inistered, rapidly-absorbed, short-acting insulinotropic agent, it is used for the treatment of type 2 diabetes mellitus.
Starlix (Novartis);Fastic;Starsis.
Although nateglinide, N-(4-isopropylcyclohexanecarbonyl)-D-phenylalanine (Starlix), belongs tothe metaglinides, it is a phenylalanine derivative and representsa novel drug in the management of type 2 diabetes.
Nateglinide (Starlix) is D-Phenylalanine, N-[[trans-4-(1-methylethyl)cyclohexyl]carbonyl]-; or (-)-N-[(trans-4-isopropylcyclohexyl)carbonyl]-D-phenylalanine. Itis noteworthy that, although nateglinide is much less potenton a dosage basis than is repaglinide and most of the sulfonylureas,this drug seems to exhibit unique molecularpharmacodynamics. Nateglinide closes ATP-sensitive K channels some threefold more rapidly than repaglinide, andexhibits an off-rate twice as fast as that of glyburide orglimepiride and five times faster than repaglinide. Thesecharacteristics are reflected by the systemic pharmacodynamicsof this drug, translating clinically to improvedsafety, among other apparent benefits.
Nateglinide is a Kir6.2/SUR1 channel inhibitor and antidiabetic. It is selective for the SUR1 subtype, which is found on pancreatic islet cells. Nateglinide evokes KATP channel-dependent insulin secretion (50-200 μM) in the absence and presence of insulin.
Approved in the United States in late 2000, nateglinide is a rapidly absorbed insulin secretagogue that has a mechanism of
action similar to that of repaglinide, with effects appearing within 20 minutes following oral dosing.
Bioavailability is 73%,
and it is 98% protein bound, primarily to albumin. Nateglinide is tissue selective, with low affinity for cardiac and skeletal
muscle.
Treatment of type 2 diabetes in combination with
metformin
Potentially hazardous interactions with other drugs
Antibacterials: concentration reduced by rifampicin.
Antifungals: hypoglycaemic effect possibly enhanced
by fluconazole.
Lipid-lowering agents: hypoglycaemic effect possibly
enhanced by gemfibrozil.
It is metabolized in the liver, with 16% excreted in the urine unchanged. The major metabolites are hydroxyl
derivatives (CYP2C9, 70%; CYP3A4, 30%) that are further conjugated to the glucuronide derivatives.
