Abstract

The aim of the study was to evaluate the effect of zinc as well as magnesium or copper ions on the efficacy of passive transport of imipramine hydrochloride in in vitro model. According to results from passive transport, the next aim of the studies was to check the efficiency of active transport of imipramine hydrochloride in the presence or absence of zinc ions. The passive transport study was conducted in specially designed capsules, while CaCo-2 cell lines were used in active transport evaluation. Zinc, magnesium and copper content was determined by F-AAS method. The analysis of imipramine hydrochloride was performed using HPLC method. Mean concentrations of zinc, magnesium, and copper ions obtained in this experiment were as follows: 2.98, 1.34 and 3.52 mg/L, respectively. The presence of zinc ions increased the efficiency of active transport of imipramine hydrochloride by 39%. Furthermore, the transport of zinc ions in the presence of imipramine hydrochloride was 27% greater than that of the zinc-containing solutions without imipramine hydrochloride. The extending of the time of experiment from 30 to 60 minutes resulted in an increase in transport efficiency of more than 10% in both cases. The efficiency of passive and active transport of imipramine hydrochloride is influenced by the presence of Mg, Zn and Cu ions. The passive transport of imipramine hydrochloride after 90 minutes of experiment was the most effective in the presence of copper and zinc ions. Further studies conducted on the CaCo-2 cell line indicated a clear positive interaction of imipramine - zinc.

Highlights

  • Scientific papers have showed that excessive activity of the glutamatergic system plays a significant role in the pathogenesis of affective disorders

  • The efficiency of passive and active transport of imipramine hydrochloride is influenced by the presence of Mg, Zn and Cu ions

  • Further studies conducted on the CaCo-2 cell line indicated a clear positive interaction of imipramine – zinc

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Summary

Introduction

Scientific papers have showed that excessive activity of the glutamatergic system plays a significant role in the pathogenesis of affective disorders. In addition to the binding site of the agonist (glutamic acid), there are binding sites for many substances modulating NMDA activity, such as magnesium(II) ion binding site responsible for blocking of ion channel and zinc(II) ion binding site responsible for inhibition of NMDA receptor activation [2]. Another ionotropic receptor for the glutamatergic system is the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) whose activation is associated with antidepressant activity [3]. Zinc(II) and Magnesium(II) ions belong to important modulators of glutamatergic transmission and may play an important role in the pathogenesis of affective disorders [3, 19,20,21,22]

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