Central I1-imidazoline receptors as targets of centrally acting antihypertensive drugs. Clinical pharmacology of moxonidine and rilmenidine.

Moxonidine and rilmenidine are moderately selective I1-receptor stimulants. The imidazoline (I1) agonists cause peripheral sympathoinhibition, triggered at the level of central nervous imidazoline receptors. Imidazoline receptor stimulants are effective antihypertensive agents with a hemodynamic profile that is attractive from a pathophysiologic point of view. The antihypertensive activity of these agents is caused by vasodilatation and reduced peripheral vascular resistance. Left ventricular end-diastolic and end-systolic volume is reduced, whereas heart rate, stroke volume, cardiac output, and pulmonary artery pressures are largely unchanged. Long-term left ventricular hypertrophy is reduced. Both drugs, when applied in a once-daily dosage schedule, appear to control hypertension in most patients. Both drugs have been compared with representative agents from the major classes of antihypertensive drugs in controlled trials and found to be equally effective in blood pressure control. The incidence and severity of side effects are lower than those for clonidine, particularly with respect to sedation. A rebound (withdrawal) phenomenon has so far not been reported for moxonidine and rilmenidine. Therefore, I1-receptor stimulants offer the possibility of developing centrally acting agents with a better side-effect profile than do the classic alpha 2-adrenoceptor stimulants.