Objective To observe the synthesis and representations of a novel Lithium isobutyrate-L-proline chelate(IsoLiPro),and investigate its pharmacokinetics and antimanic effects.Methods IsoLiPro was prepared by single solvent crystallization,and powder X-ray diffraction,hydrogen nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy were used to identify and analyze IsoLiPro.Inductively coupled plasma mass spectrometry was used to detect the content of Lithium in plasma and tissues of rats at different time points of gavage administration of IsoLiPro,and pharmacokinetic analysis was carried out.Protein electrophoresis detected the expression and activity changes of CREB,GSK-3β,Erk1/2,and BDNF signaling pathway proteins in vitro cultured HT22 cells after IsoLiPro treatment.The effect of IsoLiPro on amphetamine-induced mania-like symptoms of mice was investigated by open field experiments.Results The representation results showed that the prepared IsoLiPro molecules were different from those of Li isobutyrate and proline,and the relevant parameters indicated a monoclinic crystal structure.The mass spectrometry showed that IsoLiPro could exist in molecular form in 50％methanol aqueous solution.The pharmacokinetic results showed that there was a good linear relationship between IsoLiPro in rat plasma and there was significant difference in pharmacokinetic parameters compared with Li2CO3.The results of protein electrophoresis showed that IsoLiPro significantly increased the expression of p-GSK-3β,p-CREB,p-Erk1/2,and BDNF,and had good in vitro biological activity.IsoLiPro effectively improved the excessive exercise behavior of mice caused by amphetamines,showing better anti-manic effect,which was stronger than Li2CO3.Conclusion In this study a novel Li chelated IsoLiPro is successfully prepared and characterized,which is superior to Li2CO3 used in clinical practice in terms of pharmacokinetics and anti-manic effect.
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