Gliclazide
[CAS# 21187-98-4]

Identification

• Classification: API >> Hormone and endocrine-regulating drugs >> Pancreatic hormones and other blood sugar regulating drugs
• Name: Gliclazide
• Synonyms: 1-(3-Azabicyclo[3.3.0]oct-3-yl)-3-p-tolylsulphonylurea
• Molecular Formula: C₁₅H₂₁N₃O₃S
• Molecular Weight: 323.41
• CAS Registry Number: 21187-98-4
• EC Number: 244-260-5
• SMILES: CC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN2CC3CCCC3C2

Properties

• Solubility: 65 mg/mL (DMSO), <1 mg/mL (water)
• Melting point: 163-169 °C

Safety Data

• Hazard Symbols: GHS07;GHS08 Warning
• Risk Statements: H302-H315-H319-H335-H361
• Safety Statements: P203-P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P318-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Reproductive toxicity	Repr.	2	H361
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Acute hazardous to the aquatic environment	Aquatic Acute	1	H402
Skin corrosion	Skin Corr.	1C	H315
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Reproductive toxicity	Lact.	-	H362
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H412

Discovery and Applications

Gliclazide, a sulfonylurea compound, was discovered in the late 1960s during efforts to develop new oral hypoglycemic agents for the treatment of diabetes mellitus. Synthesized by chemists at the French pharmaceutical company Servier Laboratories, gliclazide emerged as a promising candidate due to its ability to stimulate insulin secretion from pancreatic beta cells, thereby lowering blood glucose levels. Its discovery represented a significant advancement in diabetes management.

Gliclazide is primarily used in the management of type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and impaired insulin secretion. As an oral hypoglycemic agent, gliclazide works by stimulating insulin release from pancreatic beta cells, thereby lowering blood glucose levels. It helps improve glycemic control, reduce hyperglycemia-associated symptoms, and decrease the risk of diabetes-related complications, such as cardiovascular disease, neuropathy, and nephropathy.

Gliclazide can be used as monotherapy or in combination with other antidiabetic medications to achieve target glycemic goals in patients with type 2 diabetes. When used alone, gliclazide is effective in controlling blood glucose levels, particularly in individuals who are unable to achieve adequate glycemic control through diet and exercise alone. Additionally, gliclazide is often prescribed in combination with metformin, thiazolidinediones, or other oral antidiabetic agents.

Beyond its glucose-lowering effects, gliclazide has demonstrated cardiovascular benefits in patients with type 2 diabetes. Clinical studies have shown that gliclazide treatment is associated with a reduced risk of cardiovascular events, including myocardial infarction, stroke, and cardiovascular-related mortality. These cardioprotective effects may be attributed to gliclazide's ability to improve endothelial function, reduce oxidative stress, and attenuate vascular inflammation.

Gliclazide has also been shown to exert nephroprotective effects in individuals with diabetes. Chronic hyperglycemia can lead to kidney damage and diabetic nephropathy, a common complication of diabetes characterized by proteinuria and progressive loss of renal function. Gliclazide treatment has been associated with a reduction in urinary albumin excretion and preservation of renal function in diabetic patients.

Emerging evidence suggests that gliclazide may possess neuroprotective properties, offering potential benefits in the management of diabetic neuropathy and neurodegenerative disorders. Preclinical studies have demonstrated that gliclazide can attenuate neuronal damage, reduce oxidative stress, and improve neurological function in animal models of diabetes and neurodegeneration.

References

1984. Measurement of gliclazide in plasma by radial compression reversed-phase liquid chromatography. Clinical Chemistry, 30(11).
DOI: 10.1093/clinchem/30.11.1789

2024. Adverse Events Due to Oral Hypoglycemic Drugs. Management of Diabetic Complications.
DOI: 10.1007/978-981-97-6406-8_21

2007. Comparison of the Solubility and Dissolution Rate Between Gliclazide Solid Complex and Its Nanospheres. Drug Development and Industrial Pharmacy, 33(1).
DOI: 10.1080/03639040600920622