SYNTHESIS AND HISTAMINE H-3 RECEPTOR AGONIST ACTIVITY OF MONO-SUBSTITUTED AND DIALKYL-SUBSTITUTED HISTAMINE DERIVATIVES

In search for potential histamine H-3-receptor agonists a series of mo no- and dialkyl-substituted histamine derivatives was synthesized. All target compounds were tested in vitro for their agonist activity at H -3-, H-2-, and H-1-receptors. Introduction of one ethyl or two methyl residues into histamine led to compounds with decreased histamine H-3- agonist potency in most cases. However, the non-chiral alpha,alpha-dim ethylhistamine (15) was identified to be three times as active as hist amine itself at H-3-receptors. In addition 15 Dimethylhistamine 23, wh ich is a potential metabolite of (alpha R)-alpha-methylhistamine 1, pr oved to be inactive at all three histamine receptor subtypes.