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.
D006632:Histamine; D007536:Isomerism; D011968:Receptors, Histamine / Q000187:drug effects*; D011970:Receptors, Histamine H2 / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D006632:Histamine; D013890:Thiourea