Rigid analogs of taurine as potential taurine antagonists

In this study we tested the potential taurine-antagonistic properties of three rigid analogs of taurine, 3-amino- (1), 3-hydrazino- (2) and 3-aminomethyl-1,2,4-benzothiadiazine-1,1-dioxide (3), which were prepared in our laboratory, using TAG (6-aminomethyl-3-methyl-1,2,4-benzothiadiazine-1,1- dioxide) (4), the only antagonist of taurine so far available, as reference compound in "in vivo" and "in vitro" experiments. Some physicochemical properties of (1), (2) and (3) were studied and the synthesis of TAG (4) was improved with a new preparative method. A dose-effect study performed by injecting intracerebroventricularly (1), (2) and (3) showed that these compounds have none of exciting effects exerted by the high doses of TAG (4). (1) and (3) as well as TAG (4), were found to antagonize the controlateral turning induced by the intracerebro injection of taurine and to potentiate the sedative effect of diazepam. We failed to find specific binding for taurine in different brain synaptic membrane preparations using 3H-taurine as radioligand and taurine, (1) and (3) as binding displacer. (1), (3) and TAG (4) however were found to antagonize the inhibitory effect of taurine on 3H-diazepam binding. These results seem to indicative that at least (1) and (3), which were more extensively studied than (2) because of their better solubility, are taurine antagonists with an apparent better selectivity than TAG (4).