Clonidine, moxonidine, and rilmenidine are centrally acting antihypertensive agents that lower arterial pressure by inhibiting the tonic activity of sympathoexcitatory neurons in the rostral ventrolateral medulla. Competing hypotheses have been put forward by different investigators to explain the sympathoinhibition evoked by "imidazoline drugs": either via central actions at α2-adrenergic rece...

The sympathetic nervous system plays a central role in the pathophysiology not only of hypertension and other cardiovascular diseases but also metabolic disorders including disturbances of glucose and lipid homeostasis. A centrally acting sympathetic agent is therefore attractive not only for lowering blood pressure, but also intervening with multiple disease processes. Older agents such as clo...

1 The hypotensive effect of imidazoline-like drugs, such as clonidine, was attributed both to alpha2-adrenergic receptors and nonadrenergic imidazoline receptors, which are divided into I1, I2 and I3 subtypes. 2 We have recently synthesized a derivative of (2-(2-chloro-4-iodo-phenylamino)-5-methyl-pyrroline (LNP 911), the first high-affinity and selective ligand for I1 receptors (I1R), with a p...

BACKGROUND Both alpha(2)-adrenergic and non--alpha(2)-adrenergic mechanisms seem to be involved in the hypotensive effect of imidazoline-like drugs. This study aimed at investigating how these 2 mechanisms work together to modify blood pressure (BP). METHODS AND RESULTS LNP 509, which appeared in this study to be devoid of alpha(2A)-adrenergic activity, was administered to anesthetized rabbit...

Background—Both 2-adrenergic and non– 2-adrenergic mechanisms seem to be involved in the hypotensive effect of imidazoline-like drugs. This study aimed at investigating how these 2 mechanisms work together to modify blood pressure (BP). Methods and Results—LNP 509, which appeared in this study to be devoid of 2A-adrenergic activity, was administered to anesthetized rabbits and wild-type (WT) mi...