Ganellin C R, Owen D A
Agents Actions. 1977 Mar;7(1):93-6. doi: 10.1007/BF01964887.
Burimamide, a histamine H2-receptor antagonist, has been shown to cause pressor responses in pithed rats. The response can be prevented by prior removal of the adrenal glands or by pretreatment with the alpha-adrenoceptor antagonist, phentolamine, 5 mg/kg, suggesting that the pressor response to burimamide is due to release of catecholamines from the adrenal glands. The pressor activity of burimamide has been compared with that of metiamide and two close chemical analogues, methylburimamide and thiaburimamide, in order to identify which chemical features of the compounds are necessary for this activity. Methylburimamide was the most potent pressor agent, followed by burimamide, metiamide and thiaburimamide. The pressor effects (and presumably catecholamine-releasing activities) appear to be related to the basicities of the compounds. We conclude that the release of catecholamines by these histamine H2-receptor antagonists is probably due to their cationic (imidazolium) forms.
组胺H2受体拮抗剂布立马胺已被证明可使脊髓毁损大鼠产生升压反应。预先摘除肾上腺或用5毫克/千克的α-肾上腺素能受体拮抗剂酚妥拉明预处理可预防该反应,这表明布立马胺的升压反应是由于肾上腺释放儿茶酚胺所致。为了确定化合物的哪些化学特征对该活性是必需的,已将布立马胺的升压活性与甲硫米特以及两种结构相近的化学类似物甲基布立马胺和硫布立马胺进行了比较。甲基布立马胺是最有效的升压剂,其次是布立马胺、甲硫米特和硫布立马胺。升压作用(大概还有儿茶酚胺释放活性)似乎与化合物的碱性有关。我们得出结论,这些组胺H2受体拮抗剂释放儿茶酚胺可能是由于它们的阳离子(咪唑鎓)形式。