EFFECTS OF LKYL-1,3-DIHYDRO-1-OXOISOINDOLIN-5-YL)OXY]ALKANOIC ACIDS ON CHLORIDE TRANSPORT IN PRIMARY ASTROGLIAL CULTURES

It has been demonstrated that agents which inhibit chloride influx and , therefore, lower intracellular chloride levels in the astrocyte, a m ajor cell type in the cerebral gray matter, inhibit astrocytic swellin g in vitro and in vivo. Herein, we report additional examples of a ser ies of [(N-alkyl-1,3-dihydro-1 -oxoisoindolin-5-yl)oxy] alkanoic acids and their effects upon ion transport in primary rat astrocyte culture s. The 4-chloro-substituted 1-oxoisoindolines demonstrated superior as trocytic chloride influx inhibitory activity as compared to the 6-chlo ro and nonchlorinated analogs. The four-carbon acid side chain derivat ives were more active than the three- and two-carbon analogs. The phar macological profile of these compounds was examined with respect to in hibition of the Cl--Cl-/Cl--HCO3- anion exchanger and Na+-K+-2Cl(-) co transport mechanisms in glia, and the compounds were found to exhibit a similar profile to that of furosemide by inhibiting both transporter s.