Central and peripheral alpha-adrenergic effects of some imidazolidines

The central hypotensive activity of clonidine and of 12 structurally related analogues was determined following intravenous administration to pentobarbital-anaesthetized, normotensive rats. This sympathoinhibitory action was characterized by means of a pC30, calculated from dose-response curves. The centrally mediated depressor activity (pC30) was correlated with the peripherally induced pressor activity of the compounds (pC100) reported on previously and which had been established after intravenous application to pithed rats. In these correlations, the quantitative ability of the substances to penetrate into the central nervous system had been taken into account. The octanol/buffer (pH = 7.4) partition coefficients were used as a measure of lipophilic behaviour. A positive correlation was found between the central hypotensive activity and the linear combination of peripheral alpha-sympathomimetic activity and lipophilicity.