Hypotensive and bradycardic activities of clonidine and related imidazolidines; structure-activity relationship

The hypotensive effect of clonidine and 27 of its structurally related imidazolidines, which differ in substitution in the aromatic moiety, was determined following intravenous application to pentobarbital-anaesthetized, normotensive rats. The decrease in cardiac frequency was measured at the moment of the maximal depressor effect. For all the compounds studied the same type of mechanism regarding their cardiovascular action is involved. Both the hypotensive and bradycardic effects were quantified by means of equipotent doses, calculated from dose-response characteristics constructed for each derivative. A wide range of bradycardic and hypotensive activities (greater than 4 logarithmic units) is covered by this selection of clonidine-like drugs. Moreover, a linear relationship is found between the hypotensive and bradycardic activities within the present series of compounds. The influence of structural modifications in the aromatic portion of the imidazolidines on hypotensive activity is described and discussed with respect to the structure-activity relationship (SAR) in centrally acting hypotensive imidazolidines.