Moxonidine is a centrally acting agent which binds selectively and with high affinity to imidazoline I1-receptors in the rostral ventrolateral medulla of the brainstem.16 Occupation of the imidazoline binding site by moxonidine reduces peripheral sympathetic activity, culminating in lowered peripheral arterial resistance without significant adverse change in cardiac output and pulmonary haemodynamics.17,18 The mode of action of moxonidine and its haemodynamic effects are described in more detail in the Chemistry and Mode of Action section.
Several placebo-controlled studies described in this document have demonstrated that moxonidine is as effective as other classes of antihypertensives when given as monotherapy (see table below). Clinical studies have also indicated that moxonidine can be used as an adjunct to other first-line therapies such as diuretics and ACE-inhibitors, giving significant additional blood pressure lowering effects compared with monotherapy. There is a clear dose-response effect, allowing titration of dosage to optimise the therapeutic response.
Moxonidine appears to be of particular benefit for hypertensive patients with metabolic syndrome. It has been shown to give significant improvement in glucose metabolism and insulin resistance, with a neutral effect on the lipid profile. Clinical studies also indicate that moxonidine has a renal protective effect.
Unlike older centrally-acting agents (clonidine and methyldopa), moxonidine has relatively little affinity for α2-receptors in the brainstem.16 As a result, adverse events such as sedation and dry mouth, which are in part mediated by α2-receptor interactions, are infrequently reported during prolonged therapy with moxonidine.28 There is a low potential for drug interactions.
This document starts with a review of clinical experience with moxonidine, and includes summaries of efficacy data from key clinical studies. A summary of tolerability appears after the efficacy data, followed by information on chemistry, mode of action, pharmacokinetics and dosage. The principal efficacy studies reviewed are as follows:
|Studies versus active comparators||Frei19 (vs diuretic)
Prichard20 (vs atenolol)
Lotti21 (vs captopril)
Kraft22 (vs captopril)
Küppers23 (vs enalapril)
Prichard24 (vs enalapril)
Prichard25 (vs enalapril)
Wolf26 (vs nifedipine)
Mangiameli27 (vs nifedipine)
|Insulin resistance, glucose tolerance, diabetes||Haenni31
|Renal protection, microalbuminuria, creatinine clearance||Neumann39