Moxonidine reduces sympathetic outflow of the brain
Moxonidine interacts with imidazoline I1-receptors in the rostroventrolateral medulla and thereby inhibits sympathetic outflow of the brain. This area of the brain is involved in the baroreceptor reflex which is important for adaptation of the body to postural changes. For example, a reduced venous return to the heart activates cardiopulmonary receptors leading to a rise in sympathetic outflow. Unfortunately, this mechanism adjusts to long term changes in blood pressure, i.e. baroreceptor resetting, and does not respond anymore to a pathologically raised high blood pressure, i.e. hypertension.
    It appears that moxonidine interacts with neurons within this pathway and thereby reduces sympathetic outflow. However, no effects on postural reflexes have been observed. If, however, lifestyle factors raise sympathetic outflow of the brain, moxonidine appears to downregulate the sympathetic activity by interfering with the medullar centers involved in the baroreceptor reflex.

An increased sympathetic activity not only results in hypertension but also favours insulin resistance. The chain of events is shown for the example of hypertension which often is mediated by a greater activation of peripheral alpha-1 adrenergic receptors:

A moxonidine-mediated reduction in the sympathetic outflow of the brain results in a smaller number of norepinephrine molecules released from sympathetic nerve terminals. Thus, there will be less vasoconstriction due to reduced alpha-1 adrenoceptor effects. In addition, various functions of the body such as insulin sensitivity are expected to be affected in a beneficial manner.