Studies on Histaminergic Compounds, IV Non‐isosterism between the Imidazole, Guanidino and Isothiourea Moieties at the H 2 ‐Receptor

S,S'‐Alkylenediisothioureas were found to show only weak agonistic or antagonistic H 2 ‐activity, depending on the length of the alkylene chain. Introduction of a substituent in the amidino parts of both isothiourea groups resulted in a complete loss of the agonistic activity; only inactive compounds or weakly active H 2 ‐antagonists were obtained. Replacing one of the isothiourea groups of the alkylenediisothioureas with n = 2, 3 or 4 by a guanidino group has hardly any or no effect at all on the histamine H 2 ‐activity on the guinea‐pig right atrium. However, extending the alkylene chain of these guanidylalkylisothioureas to n = 5 and 6 results in a strong increase in the H 2 ‐agonistic activity.