Blonanserin N-Oxide Lowers Glucose Levels in Animal Models

Maddileti D,Kona K,Mannava C,Rao Khandavilli Ub,Nangia A,Ernest K,Konga Db,Mummareddy S,Medipelli Sr,Swapna B,Vangalapudi L,Tejpal R,Kokkonda V

doi:10.15744/2348-9782.4.102

Abstract

Blonanserin N-Oxide Lowers Glucose Levels in Animal Models

Highlights

Type-2 Diabetes mellitus (DM) is a metabolic disorder caused by insulin resistance and obesity
Oral glucose tolerance test on Wistar rats confirmed the potential of Blonanserin N-oxide (BLNO) to reduce glucose levels at 5 mpk dose, comparable to that of marketed drugs metformin HCl (MHCL) and sitagliptin phosphate monohydrate (SPMH) at 100 mpk dose in 90-120 min after drug administration
The glucagon like peptide (GLP-1 and 2) are natural incretin hormones which are released from the gut in response to food intake, and they are collectively responsible for glucose-dependent insulin release [7]

Summary

Introduction

Type-2 Diabetes mellitus (DM) is a metabolic disorder caused by insulin resistance (dysfunction of pancreatic beta cells) and obesity. One way to address the problem is to target pancreatic β-cells for increasing endogenous insulin levels via small molecule drugs (bigunides, sulfonylureas, meglitinides, thiazolidinediones, alpha-glucosidase inhibitors, dipeptidyl-peptidase IV inhibitors, incretin-based therapies, etc.) [2,3,4]. A recent study showed that phosphorylation of M3-muscarinic receptor plays an important mechanistic role in facilitating insulin release from pancreatic islets by coupling of the receptor to protein kinase D1 [12] These muscarinic acetylcholine receptors are a subfamily of GPCRs recognizing the neurotransmitter acetylcholine and signaling through G proteins of the Gq/11 class. The pharmacological effects of CLNO are fundamentally different compared to previous drug classes, in that it activates insulin secretion instantaneously and increases the size and mass of the pancreatic islet β-cells [15]. Based on the structural similarity of these two molecules (Figure 1), we undertook the synthesis of the natural metobolite BLNO and to screen its anti-diabetic activity

Materials and Methods

Results and Discussion

Conclusion