Centrally acting drugs for reducing sympathetic outflow of the brain
Moxonidine is a centrally acting drug which exhibits an imidazoline ring. Moxonidine binds to imidazoline I1- receptors of the rostral ventrolateral medulla of the brain stem.
 


Since moxononidine has a high affinitiy for imidazoline receptors, it greatly differs from first generation centrally acting antisympathotonic drugs. Moxonidine of  Abbott  has the highest selectivity for I1-imidazoline receptors. Since adverse events of clonidine and guanabenz are mainly mediated by presynaptic alpha-2 receptors, it is not unexpected that moxonidine has a low incidence of side effects.
 

A comparison of the selectivity of centrally acting antihypertensive drugs of the "first generation" and "second generation" for  I1-imidazoline receptors and alpha-2 receptors (1) in the rostral ventrolateral medulla of the brain (RVLM) (2):
 
 
"First generation" centrally acting drugs

K1 for I1 (nM) K1 for alpha-2 (nM) Selectivity (I1/Alpha-2)
Guanabenz >10000 7.2 <0.0007
Guanfacine 2500 2.3 0.0009
Lofexidine 1.9 6.9 3.6
Clonidine 1.0 3.8 3.8
"Second generation" centrally acting drugs

K1 for I1 (nM) K1 for alpha-2 (nM) Selectivity (I1/Alpha-2)
Rilmenidine 5.3 113 21
Moxonidine 2.3 76 33

1. Schäfer SG, Kaan EC, Christen MO, Löw-Kröger A, Mest HJ, Molderings GJ: Why imidazoline receptor modulator in the treatment of hypertension? Ann N Y Acad Sci 1995;763:659-672

2. Reis DJ: The rostral ventrolateral medulla: a target of therapy for hypertension. Risk Factors 1995;5(suppl. 1):11-18