A quantitative analysis method for a new glycogen synthase kinase-3 inhibitor and its pharmacokinetics in rats

Alzheimer's disease (AD), as a chronic and frequent neurodegenerative disease in the elderly population, has caused a huge economic burden to society, family, and other aspects. (E)-N-(4-(((2-amino-5-phenylpyridin-3-yl) imino) methyl) pyridine-2-yl) cyclopropanecarboxamide (PIMPC), a new glycogen synthase kinase-3 (GSK-3) inhibitor, has been designed and synthesized as a potential anti-AD compound with antioxidant and metal chelating properties. In this study, we established an HPLC method for the determination of PIMPC, which has high accuracy, good sensitivity, and repeatability. This method determined the PIMPC content in rat plasma at different time points after intragastric administration to understand the pharmacokinetics (PK) process of PIMPC in rats. In addition, we preliminarily evaluated the effect of PIMPC on the liver and kidney in rats at pharmacodynamic doses. In conclusion, we have established a quantitative analysis method for PIMPC with excellent performance. And the PK process of PIMPC in rats, which was characterized by fast absorption, rapid distribution, and rapid elimination, conformed to the characteristics of the two-compartment model. In addition, long-term administration of PIMPC at therapeutic doses would not affect liver and kidney function. These studies have a certain reference for the development and research of PIMPC as a potential anti-AD drug.

Alzheimer's disease; HPLC; glycogen synthase kinase-3 inhibitor; pharmacokinetics.