Dimaprit, (S-[3-(N,N-dimethylamino)propyl]isothiourea). A Highly Specific Histamine H2-receptor Agonist. Part 2. Structure-activity Considerations

Dimaprit, S-[3-(N,N-dimethylamino)propyl]isothiourea, appears to be a highly specific histamine H2-receptor agonist. Further indications of specificity are obtained from chemical considerations. Dimaprit has two basic centres (pKa values respectively 8.23 and 9.23, at 40 degrees) and at pH 7.4 about 5% of the molecules will be present as the monocation analogous to histamine monocation. Chemical comparison suggests that the --N+HMe2 group corresponds to the --N+H3 of histamine, and that the isothiourea group of dimaprit (which can undergo 1,3-prototropic tautomerism) may simulate the imidazole ring of histamine and function as a proton transfer agent at H2 receptors. Simple structural analogues of dimaprit are only weakly active, indicating a high degree of chemical specificity for H2-receptor stimulation; such compounds (e.g. the lower homologue, SK & F 91487) may serve as useful chemical controls when studying the actions of dimaprit.