Stimulation of the imidazoline I1-receptor represents a new mode of antihypertensive action, inhibiting peripheral α-adrenergic tone by a central mechanism. Moxonidine is an imidazoline I1-receptor modulator. Acute hemodynamic studies indicate that moxonidine results in an acute fall of both blood pressure and systemic vascular resistance, whereas heart rate, cardiac output, stroke volume, and pulmonary artery pressures are not affected. The ejection fraction is not significantly affected. Left ventricular end-systolic and -diastolic volumes are reduced. There is regression of left ventricular hypertrophy after 6 months of treatment. Epinephrine, norepinephrine, and renin levels are all reduced, a finding consistent with central inhibition of sympathetic tone. After oral administration Tmax is about 1 h and bioavailability approaches 90%. Moxonidine is mostly excreted unchanged; biotransformation is unimportant. The T1/2 is 2.5 h, prolonged by renal insufficiency. The antihypertensive effect lasts longer than would be expected from the halflife, suggesting possible retention in the CNS. Open studies with moxonidine have revealed decreases on the order of 20-30 mm Hg systolic and 10-20 mm Hg diastolic blood pressure. Most patients are controlled by 0.2-0.4 mg daily. Moxonidine has been compared with representatives from each important class of antihypertensive drugs, with diuretics, clonidine, calcium antagonists, angiotensin-converting enzyme inhibitors, and both α- and β- blocking drugs. Blood pressure control has been similar with moxonidine and these other agents. The overall incidence of side effects was similar, although moxonidine has a lower incidence of side effects than clonidine. Meta-analysis of controlled studies with moxonidine indicates that moxonidine causes similar decreases in blood pressure in both male and female subjects, in those below 50 years, those 50-60 years, and those over 60 years old, regardless of body weight. As with some other drugs, higher systolic blood pressure are associated with larger falls of systolic blood pressure, and the same is true for diastolic blood pressure.