Cl. Waller et al., EFFECTS OF LKYL-1,3-DIHYDRO-1-OXOISOINDOLIN-5-YL)OXY]ALKANOIC ACIDS ON CHLORIDE TRANSPORT IN PRIMARY ASTROGLIAL CULTURES, Journal of pharmaceutical sciences, 83(4), 1994, pp. 571-576
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.