The pressor activity of burimamide: a relationship between chemical constitution and pressor activity of burimamide and related histamine H2-receptor antagonists

Abstract

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.