Mechanisms of NMDA Receptor Inhibition by Biguanide Compounds DOI Creative Commons

Arseniy S. Zhigulin,

Anastasiya O. Novikova,

Oleg I. Barygin

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(9), P. 1234 - 1234

Published: Sept. 19, 2024

N-methyl-D-aspartate (NMDA) receptors are inhibited by many medicinal drugs. The recent successful repurposing of NMDA receptor antagonists ketamine and dextromethorphan for the treatment major depressive disorder further enhanced interest in this field. In work, we performed a screening activity against native rat CA1 hippocampal pyramidal neurons among biguanide compounds using whole-cell patch-clamp method. Antimalarial biguanides proguanil cycloguanil, as well hypoglycemic phenformin, them micromolar concentrations, while another metformin antiviral moroxydine were practically ineffective. IC50 values at −80 mV holding voltage 3.4 ± 0.6 µM 9.0 2.2 13 1 phenformin. inhibition all three was not competitive. Cycloguanil acted an voltage-dependent trapping channel blocker, phenformin allosteric inhibitors. Our results support potential clinical neurodegenerative disorders linked to glutamatergic excitotoxicity also providing better understanding structural determinants antagonism biguanides.

Language: Английский

Stimuli‐Responsive Nano Drug Delivery Systems for the Treatment of Neurological Diseases DOI Open Access
Xi‐jian Dai, Weilong Li, Dongdong Xie

et al.

Small, Journal Year: 2025, Volume and Issue: 21(9)

Published: Jan. 22, 2025

Abstract Nanomaterials with unparalleled physical and chemical attributes have become a cornerstone in the field of nanomedicine delivery. These materials can be engineered into various functionalized nanocarriers, which focus research. Stimulus‐responsive nanodrug delivery systems (SRDDS) stand out as sophisticated class nanocarriers that release drugs response to environmental cues. Due complex pathogenesis multifaceted pathological environment nervous system, developing accurate effective drug therapy low side‐effects is formidable task. In recent years, SRDDS been widely used treatment neurological diseases. By customizing align specific microenvironment system tissues or external stimulation, efficacy enhanced. This review provides an in‐depth look at characteristics diseases highlights case studies tailored treat these disorders based on unique stimulation criteria triggers. Additionally, this comprehensive overview progress future prospects technology diseases, providing valuable guidance for its transition from fundamental research clinical application.

Language: Английский

Citations

0
Mechanisms of NMDA Receptor Inhibition by Biguanide Compounds DOI Creative Commons

Arseniy S. Zhigulin,

Anastasiya O. Novikova,

Oleg I. Barygin

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(9), P. 1234 - 1234

Published: Sept. 19, 2024

N-methyl-D-aspartate (NMDA) receptors are inhibited by many medicinal drugs. The recent successful repurposing of NMDA receptor antagonists ketamine and dextromethorphan for the treatment major depressive disorder further enhanced interest in this field. In work, we performed a screening activity against native rat CA1 hippocampal pyramidal neurons among biguanide compounds using whole-cell patch-clamp method. Antimalarial biguanides proguanil cycloguanil, as well hypoglycemic phenformin, them micromolar concentrations, while another metformin antiviral moroxydine were practically ineffective. IC50 values at −80 mV holding voltage 3.4 ± 0.6 µM 9.0 2.2 13 1 phenformin. inhibition all three was not competitive. Cycloguanil acted an voltage-dependent trapping channel blocker, phenformin allosteric inhibitors. Our results support potential clinical neurodegenerative disorders linked to glutamatergic excitotoxicity also providing better understanding structural determinants antagonism biguanides.

Language: Английский

Citations

1