Moxonidine displays a presynaptic alpha-2-adrenoceptor-dependent synergistic sympathoinhibitory action at imidazoline-1 receptors.

The function of presynaptic imidazoline-1 receptors (I1-R) in the heart remains unclear. In rat hearts, UK14.304 and moxonidine reduced norepinephrine (NE) release.

Presynaptic effects of moxonidine in isolated buffer perfused rat hearts: role of imidazoline-1 receptors and alpha2-adrenoceptors.

Numerous studies support the concept that centrally acting antihypertensive drugs, such as imidazolines, mediate sympathoinhibition not only via activation of central nervous alpha2-adrenoceptors (alpha2-AR) but also via imidazoline-1 receptors (I1-R). An additional presynaptic involvement in sympathetic neurotransmission of imidazolines, via I1-R independent of alpha2-AR, is still controversial and remains to be clarified in the heart. Concentration response curves on endogenous norepinephrine (NE) overflow evoked by stimulation of epicardial postganglionic sympathetic nerves in isolated buffer-perfused rat hearts were performed for brimonidine, moxonidine, rauwolscine, 2-endo-amino-3-exo-isopropylbicyclo[2.