Effects of [(N-alkyl-1,3-dihydro-1-oxoisoindolin-5-yl)oxy]alkanoic acids on chloride transport in primary astroglial cultures

Article abstract of DOI:10.1002/jps.2600830426

It has been demonstrated that agents which inhibit chloride influx and, therefore, lower intracellular chloride levels in the astrocyte, a major cell type in the cerebral gray matter, inhibit astrocytic swelling in vitro and in vivo. Herein, we report additional examples of a series of [(N-alkyl-1,3- dihydro-1-oxoisoindolin-5-yl)oxy]alkanoic acids and their effects upon ion transport in primary rat astrocyte cultures. The 4-chloro-substituted 1- oxoisoindolines demonstrated superior astrocytic chloride influx inhibitory activity as compared to the 6-chloro and non-chlorinated analogs. The four- carbon acid side chain derivatives were more active than the three- and two- carbon analogs. The pharmacological profile of these compounds was examined with respect to inhibition of the Cl^--Cl^-/Cl^--HCO₃^- anion exchanger and Na⁺-K⁺-2Cl cotransport mechanisms in glia, and the compounds were found to exhibit a similar profile to that of furosemide by inhibiting both transporters.