Improving Lithium Therapeutics by Crystal Engineering of Novel Ionic Cocrystals
Autor: | Brian Giunta, Lukasz Wojtas, Naga Kiran Duggirala, R. Douglas Shytle, Jared Ehrhart, Michael J. Zaworotko, Seol-Hee Kim, Adam J. Smith, Jingji Jin, Jun Tan |
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Rok vydání: | 2013 |
Předmět: |
Stereochemistry
Pharmaceutical Science Ionic bonding chemistry.chemical_element Lithium Nitric Oxide Crystal engineering Hippocampus Article Cell Line Food and drug administration Glycogen Synthase Kinase 3 Mice chemistry.chemical_compound Neural Stem Cells Cell Line Tumor Drug Discovery Animals Technology Pharmaceutical Phosphorylation cocrystals bipolar disorder Ions Therapeutic window Glycogen Synthase Kinase 3 beta Chemistry Lithium carbonate Cell Differentiation Nitric oxide metabolism Combinatorial chemistry Rats gsk-3 Molecular Medicine Microglia pharmacokinetics |
Zdroj: | Molecular Pharmaceutics |
ISSN: | 1543-8392 1543-8384 |
Popis: | Current United States Food and Drug Administration (FDA)-approved lithium salts are plagued with a narrow therapeutic window. Recent attempts to find alternative drugs have identified new chemical entities, but lithium's polypharmacological mechanisms for treating neuropsychiatric disorders are highly debated and are not yet matched. Thus, re-engineering current lithium solid forms in order to optimize performance represents a low cost and low risk approach to the desired therapeutic outcome. In this contribution, we employed a crystal engineering strategy to synthesize the first ionic cocrystals (ICCs) of lithium salts with organic anions. We are unaware of any previous studies that have assessed the biological efficacy of any ICCs, and encouragingly we found that the new speciation did not negatively affect established bioactivities of lithium. We also observed that lithium ICCs exhibit modulated pharmacokinetics compared to lithium carbonate. Indeed, the studies detailed herein represent an important advancement in a crystal engineering approach to a new generation of lithium therapeutics. |
Databáze: | OpenAIRE |
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