The cationic-amphiphilic 2-substituted histamines, 2-(3-chlorophenyl) histamine (2-[2-(3- chlorophenyl)-1H-imidazol-4-yl] ethanamine) and 2-(2-cyclohexylethyl) histamine, activate pertussis toxin-sensitive guanine nucleotide-binding proteins (G-proteins) of the Gi- subfamily by a receptor-independent mechanism. We studied structure-activity relationships of 2-substituted histamine derivatives for this G-protein activation using six known and 12 ...