Comparative analysis of effects of imidazoline drugs on isolated rat heart atria.

Effects of cumulative concentrations of 16 known imidazoline and 2 imidazole drugs on amplitude and rate of spontaneously beating isolated rat heart atria were measured and related to the respective effects induced by norepinephrine. In addition, the effects of fixed concentrations of the agents on the responses evoked by cumulative concentrations of norepinephrine were determined. In general, imidazolines classified as alpha 1-adrenoceptor agonist showed positive inotropic activity providing evidence for involvement of the alpha 1-adrenoceptor in mediating cardiac contractility. Negative chronotropic effect was common for the imidazolines studied, including alpha 1-adrenoceptor agonists, alpha 2-adrenoceptor agonists, alpha 1/alpha 2-adrenoceptor antagonists and antazoline--an antihistaminergic imidazoline devoid of adrenoceptor affinity. On the other hand, the imidazole derivative, medetomidine, showed a weak positive chronotropic activity. Negative chronotropic properties appeared to be independent of the alpha-adrenoceptors and may result from the membrane stabilizing action, involving probably the sodium channel blockade.