Drugs acting on imidazoline receptors: a review of their pharmacology, their use in blood pressure control and their potential interest in cardioprotection

Abstract

Drugs acting within the autonomic nervous system are of particular interest when autonomic abnormalities are implicated in the development and maintenance of various cardiovascular pathologies. For example, it has been documented that in the early stages of hypertensive disease, i.e. hyperkinetic borderline hypertension, a sympathetic hyperactivity associated with a decreased parasympathetic activity results in increased cardiac output and heart rate. Several classes of drugs acting within the central, as well as the peripheral, autonomic nervous system are very efficient in treating hypertensive disease. One class - the second generation of a group of centrally acting drugs selective for imidazoline receptors - has proved beneficial in this respect, because drugs in this class are well tolerated and have interesting additional effects such as their antiarrhythmic action. Rilmenidine and moxonidine are the lead compounds of this class of drugs. Rilmenidine and moxonidine both proved more selective for cerebral imidazoline receptors than the reference drug, clonidine. It was suggested that this selectivity, attributable to their lower affinity for alpha2-adrenoceptors, explains the low incidence of adverse effects (including sedation) associated with these drugs. In addition, potentially beneficial actions on cardiac dysrythmias and congestive heart failure enlarge the therapeutic potential of the second generation of imidazoline-related drugs. This review focuses on the main pharmacological and clinical properties of rilmenidine and moxonidine, paying particular attention not only to their efficacy in hypertension but also to other potential cardiovascular indications.