Saxagliptin 361442-04-8

Introduction of Saxagliptin :

 

Saxagliptin is an orally active hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs.This compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.

 

Specification of Saxagliptin :

 

Test	Specifications	Result
Assay  Content % by HPLC	Min.98%	99.08%
Appearance	white powder	Complies
Odor	Characteristic	Complies
PH	5.0-7.0	6.09
Clarity of water solution	Transparent, colorless, none suspended matters	Complies
Loss on drying %	MAX 0.5	0.25
Ash %	MAX.0.5	0.38
Melting point	+202.0-212.0°C	Complies
Specific rotation	+174.0-+186.0	+181.0
Hydroquinone	Negative	Complies
Heavy metals PPM	MAX.10	Complies
As          AAS Pb         Cd	<2ppm <1ppm <1ppm	Complies Complies Complies
Microbiology Total Plate Count Yeast & Mold E.Coli S. Aureus Salmonella	<1000cfu/g <100cfu/g Negative Negative Negative	122 cfu/g  13 cfu/g Complies Complies Complies
Conclusion	Conform with specification

 

Function of Saxagliptin :

 

Pharmacodynamics:

 

Post-administration of saxagliptin, GLP-1 and GIP levels rise up to 2- to 3- fold. Because it is very selective of DPP-4 inhibition, there are fewer systemic side effects. Saxagliptin inhibits DPP-4 enzyme activity for a 24-hour period. It also decreased glucagon concentrations and increased glucose-dependent insulin secretion from pancreatic beta cells. The half maximal inhibitory concentration (IC50) is 0.5 nmol/L. Saxagliptin did not prolong the QTc interval to a clinically significant degree.

 

Mechanism of Action:

 

Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor antidiabetic for the treatment of type 2 diabetes. DPP-4 inhibitors are a class of compounds that work by affecting the action of natural hormones in the body called incretins. Incretins decrease blood sugar by increasing consumption of sugar by the body, mainly through increasing insulin production in the pancreas, and by reducing production of sugar by the liver. [Bristol-Myers Squibb Press Release] DPP-4 is a membrane associated peptidase which is found in many tissues, lymphocytes and plasma. DPP-4 has two main mechanisms of action, an enzymatic function and another mechanism where DPP-4 binds adenosine deaminase, which conveys intracellular signals via dimerization when activated. Saxagliptin forms a reversible, histidine-assisted covalent bond between its nitrile group and the S630 hydroxyl oxygen on DPP-4. The inhibition of DPP-4 increases levels active of glucagon like peptide 1 (GLP-1), which inhibits glucagon production from pancreatic alpha cells and increases production of insulin from pancreatic beta cells.