Synthesis of 1,2-benzisothiazole derivatives and investigation of their putative histaminergic activity

Some new 2-(1,2-benzisothiazol-3-yl)ethylamine derivatives were synthesised and their putative histaminergic activity was investigated in in vitro gas trointestinal and cardiac preparations. In the isolated guinea pig duodenum , all the compounds induced a tetrodotoxin- and atropine-sensitive contract ile activity, which was minimally affected by mepyramine in the case of the compound 2-(1,2-benzisothiazol-3-yl)ethylamine. In the same tissue, all th e compounds were devoid of any H-3 receptor agonistic or antagonistic activ ity, but caused a nicotinic and/or 5-HT3 receptor activation. None of these compounds induced any histamine H-2 agonistic or antagonistic activity in the isolated guinea pig gastric mucose or in the isolated papillary muscle. On this latter substrate, the compound N,N,N-trimethyl-2-(1,2-benzisothiaz ol-3-yl)ethylammonium iodide induced a positive inotropic activity, apparen tly due to a release of catecholamines. These results demonstrate the subst antial inability of 1,2-benzisothiazole derivatives to interact with histam ine receptors in functional tests. These compounds, however, possess gangli omimetic properties, related to the activation of 5HT(3) and/or nicotinic r eceptors, (C) 1999 Elsevier Science S.A. All rights reserved.