Morini G, Pozzoli C, Adami M, Poli E, Coruzzi G
Dipartimento Farmaceutico, Università degli Studi di Parma, Facoltà di Farmacia, Italy.
Farmaco. 1999 Nov-Dec;54(11-12):740-6. doi: 10.1016/s0014-827x(99)00093-2.
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.
合成了一些新的2-(1,2-苯并异噻唑-3-基)乙胺衍生物，并在体外胃肠道和心脏制剂中研究了它们假定的组胺能活性。在离体豚鼠十二指肠中，所有化合物均诱导出一种对河豚毒素和阿托品敏感的收缩活性，就化合物2-(1,2-苯并异噻唑-3-基)乙胺而言，该活性受美吡拉敏的影响最小。在同一组织中，所有化合物均无任何H3受体激动或拮抗活性，但可引起烟碱样和/或5-HT3受体激活。这些化合物在离体豚鼠胃黏膜或离体乳头肌中均未诱导任何组胺H2激动或拮抗活性。在后者的底物上，化合物碘化N,N,N-三甲基-2-(1,2-苯并异噻唑-3-基)乙铵诱导出正性肌力活性，显然是由于儿茶酚胺的释放。这些结果表明，在功能测试中，1,2-苯并异噻唑衍生物基本上无法与组胺受体相互作用。然而，这些化合物具有拟神经节特性，与5HT3和/或烟碱样受体的激活有关。
