The previously proposed models for the recognition and activation of 5-HT and histamine-H2 receptors, which were employed to explain the antagonist activity of LSD at both of these receptors, as well as the selective antagonism for H2 receptors by SKF-10856 and 9,10-dihydro-LSD, are used herein to design a compound to test the H2-receptor model. The design strategy attempts to construct a compound with potentially selective H2 agonism. The design scheme maintains features which were previously used to explain selective recognition of SKF-10856 and 9,10-dihydro-LSD as well as reintroduces the chemical features proposed to be responsible for H2 activation. The existence of the H2 recognition and activation features in the proposed compound is verified, in a previously proposed model, by computational studies of the molecular electrostatic potentials and shifts in the tautomeric preference.