DIMAPRIT, [S-[3-(N,N-DIMETHYLAMINO)PROPYL]ISOTHIOUREA] - A HIGHLY SPECIFIC HISTAMINE H-2-RECEPTOR AGONIST .2. STRUCTURE-ACTIVITY CONSIDERATIONS

Dimaprit, S-[3-(N,N-dimethylamino)propyl]isothiourea, appears to be a highly specific histamine H-2-receptor agonist. Further indications of specificity are obtained from chemical considerations. Dimaprit has t wo 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 monoc ation analogous to histamine monocation. Chemical comparison suggests that the -N+HMe(2) group corresponds to the -N+H-3 of histamine, and t hat the isothiourea group of dimaprit (which can undergo 1,3-prototrop ic tautomerism) may simulate the imidazole ring of histamine and funct ion as a proton transfer agent at H-2 receptors. Simple structural ana logues of dimaprit are only weakly active, indicating a high degree of chemical specificity for H-2-receptor stimulation; such compounds (e. g. the lower homologue, SK&F 91487) may serve as useful chemical contr ols when studying the actions of dimaprit.