Effect of new and known 1,4-dihydropyridine derivatives on blood glucose levels in normal and streptozotocin-induced diabetic rats

Cell Biochemistry and Function
Janïna BriedeGunars Duburs

Abstract

Analysis of the effect of several 1,4-DHP Ca(2+) channel antagonists on experimental and clinical diabetes shows that structurally similar Ca(2+) channel antagonists can exert opposite effects on Ca(2+) influx, glucose homeostasis and insulin secretion. The influence of the Ca(2+) channel antagonists on pancreatic beta cell functions is dependent on lipophilicity, interactions with the cell membrane lipid bilayer, with SNAREs protein complexes in cell and vesicle membranes, with intracellular receptors, bioavailability and time of elimination from several organs and the bloodstream. In the present work we studied the effect at several doses of new compounds synthesized in the Latvian Institute of Organic Synthesis on blood glucose levels in normal and STZ-induced diabetic rats. The compounds tested were: 1,4-DHP derivatives cerebrocrast (1), etaftoron (2), OSI-1190 (3), OSI-3802 (4), OSI-2954 (5) and known 1,4-DHP derivatives: niludipine (6), nimodipine (7) and nicardipine (8) which possess different lipophilicities. Analysis of the structure-function relationships of the effect of 1,4-DHP derivatives on glucose metabolism showed that cerebrocrast could evoke qualitative differences in activity. Insertion of an OCHF(2) group in...Continue Reading

Citations

Nov 26, 2009·Canadian Journal of Physiology and Pharmacology·Mária DrígelováLubica Lacinová
Sep 5, 2009·Drug Discovery Today·Najmeh EdrakiRamin Miri
Aug 16, 2005·Mitochondrion·Maria A S FernandesJoaquim A F Vicente
Jul 5, 2013·Journal of Pharmacological Sciences·Raquel Gómez-PliegoRafael Villalobos-Molina

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