Aminomethyl-1,2,4-benzothiadiazines as potential analogues of gamma-aminobutyric acid. Unexpected discovery of a taurine antagonist.
A series of 6- and 8-(aminomethyl)-4H-1,2,4-benzothiadiazine 1,1-dioxides has been synthesized and tested for interaction with various GABA systems. None of the compounds showed significant GABA-mimetic properties, but unexpectedly, compound 7 [6-(aminomethyl)-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide] possessed the properties of a selective antagonist of taurine, as measured by the antagonism of taurine-induced inhibition of rat cerebellar Purkinje firing.
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000818:Animals; D001581:Benzothiadiazines / Q000138:chemical synthesis* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D011963:Receptors, GABA-A; D013574:Synaptosomes / Q000378:metabolism; D013654:Taurine / Q000037:antagonists & inhibitors*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001581:Benzothiadiazines; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D013654:Taurine; D005680:gamma-Aminobutyric Acid; C032946:6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide; D000612:4-Aminobutyrate Transaminase