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

Drugs acting within the autonomic nervous system are of particular interest when autonomic abnormalities are implicated in the development and mainten ance of various cardiovascular pathologies. For example, it has been docume nted that in the early stages of hypertensive disease, i.e. hyperkinetic bo rderline hypertension, a sympathetic hyperactivity associated with a decrea sed parasympathetic activity results in increased cardiac output and heart rate. Several classes of drugs acting within the central, as well as the pe ripheral, autonomic nervous system are very efficient in treating hypertens ive disease, One class - the second generation of a group of centrally acti ng drugs selective for imidazoline receptors - has proved beneficial in thi s respect, because drugs in this class are well tolerated and have interest ing 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 th an the reference drug, clonidine. It was suggested that this selectivity, a ttributable to their lower affinity for az-adrenoceptors, explains the low incidence of adverse effects (including sedation) associated with these dru gs. In addition, potentially beneficial actions on cardiac dysrythmias and congestive heart failure enlarge the therapeutic potential of the second ge neration of imidazoline-related drugs. This review focuses on the main phar macological and clinical properties of rilmenidine and moxonidine, paying p articular attention not only to their efficacy in hypertension but also to other potential cardiovascular indications.