Imidazoline Receptor I1

The I1-imidazoline receptor is a specific, high-affinity cell-surface receptor that mediates the antihypertensive effects of certain centrally acting drugs, such as moxonidine and rilmenidine. It is distinct from α2-adrenergic receptors, although some ligands (e.g., clonidine) can interact with both. The precise molecular identity of the I1-imidazoline receptor remains under investigation. It appears to be a G protein-coupled receptor (GPCR) localized on the plasma membrane. It is found in neurons within the reticular formation and dorsomedial medulla oblongata (notably in the rostral ventrolateral medulla or RVLM), adrenal medulla, renal epithelium, pancreatic islets, platelets, and prostate. Activation leads to production of diacylglycerol (DAG), likely via direct activation of phosphatidylcholine-selective phospholipase C. Its signaling shares similarities with neurocytokine receptors like interleukins. Animal studies show that selective activation improves not only blood pressure but also metabolic parameters such as glucose tolerance—effects not seen with α2 agonists alone.

Central inhibition of sympathetic outflow.