title: Synthesis of 1,2-benzisothiazole derivatives and investigation of their putative histaminergic activity.
abstract: Some new 2-(1,2-benzisothiazol-3-yl)ethylamine derivatives were synthesised and their putative histaminergic activity was investigated in in vitro gastrointestinal and cardiac preparations. In the isolated guinea pig duodenum, all the compounds induced a tetrodotoxin- and atropine-sensitive contractile 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 the compounds were devoid of any H3 receptor agonistic or antagonistic activity, but caused a nicotinic and/or 5-HT3 receptor activation. None of these compounds induced any histamine H2 agonistic or antagonistic activity in the isolated guinea pig gastric mucosa or in the isolated papillary muscle. On this latter substrate, the compound N,N,N-trimethyl-2-(1,2-benzisothiazol-3-yl)ethylammonium iodide induced a positive inotropic activity, apparently due to a release of catecholamines. These results demonstrate the substantial inability of 1,2-benzisothiazole derivatives to interact with histamine receptors in functional tests. These compounds, however, possess gangliomimetic properties, related to the activation of 5HT3 and/or nicotinic receptors.
authors.affiliation: Dipartimento Farmaceutico, Università degli Studi di Parma, Facoltà di Farmacia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Morini
authors.forename: C
authors.initials: C
authors.lastname: Pozzoli
authors.forename: M
authors.initials: M
authors.lastname: Adami
authors.forename: E
authors.initials: E
authors.lastname: Poli
authors.forename: G
authors.initials: G
authors.lastname: Coruzzi
mesh_terms: D000818:Animals; D004386:Duodenum / Q000187:drug effects / Q000502:physiology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D006634:Histamine H1 Antagonists; D013844:Thiazoles