Nordidemnin potently inhibits inositol uptake in cultured astrocytes and dose-dependently augments lithium's proconvulsant effect in vivo.

Abstract

It has been suggested that inositol uptake across the cell membrane is of importance for maintenance of the inositol pool involved in lithium's therapeutic effect in bipolar disease and in the lithium-pilocarpine seizure test in freely moving rats (measuring the latency of a normally subconvulsive concentration of pilocarpine to seizure induction in the additional presence of lithium). We have tested this hypothesis by: 1) demonstrating an extremely high potency of nordidemnin as an inhibitor of myo-inositol uptake in primary cultures of mouse astrocytes; and 2) determining the dose-response correlation of a nordidemnin-induced decrease in the latency before appearance of seizures in the lithium-pilocarpine test after intracerebroventricular injection of minute samples (10 microl) of virtually isotonic saline solution.

• Authors: M Wolfson, H Einat, Y Bersudsky, V Berkin, R H Belmaker, L Hertz
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 60 Issue 1 Pg. 116-21 (Apr 01 2000) ISSN: 0360-4012 [Print] United States
• PMID: 10723074 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 Wiley-Liss, Inc.

Chemical References

• Antimanic Agents
• Convulsants
• Depsipeptides
• Peptides, Cyclic
• nordidemnin B
• Inositol
• Lithium Chloride

Topics

• Animals
• Antimanic Agents (pharmacology)
• Astrocytes (metabolism)
• Cells, Cultured
• Convulsants (pharmacology)
• Depsipeptides
• Drug Interactions
• Inositol (antagonists & inhibitors, metabolism)
• Lithium Chloride (pharmacology)
• Mice
• Peptides, Cyclic (pharmacology)
• Rats
• Rats, Sprague-Dawley