Importance of imidazoline receptors in the cardiovascular responses to clonidine and rilmenidine in conscious rabbits.

The present paper summarizes our studies concerning the involvement of imidazoline and alpha 2-adrenoceptors in the cardiovascular actions of centrally acting drugs rilmenidine, clonidine and methyldopa. We have found that they produce very similar cardiovascular autonomic effects which relate directly to the function of central monoamine neurotransmitters. They mimic certain elements of the noradrenergic neuron system in the central nervous system, in particular the brainstem actions which involve hypotension, bradycardia and resetting of the baroreceptor heart rate reflex. By contrast they turn off serotonergic pathways that are pressor, produce tachycardia and inhibit the baroreceptor heart rate reflex. Recent studies using specific receptors antagonist drugs idazoxan and 2-methoxy-idazoxan indicate that in conscious rabbits the imidazoline receptor actions of rilmenidine is of primary importance at doses which would be considered clinically relevant. We further conclude that the alpha 2-adrenoceptors and the imidazoline receptors are likely to be located in series i.e. along the same cardiovascular autonomic pathways in the brainstem but presumably at different sites.