[¹²⁵I]2-(2-Chloro-4-iodo-phenylamino)-5-methyl-pyrroline (LNP 911), a High-Affinity Radioligand Selective for I₁Imidazoline Receptors

Abstract

The I 1 subtype of imidazoline receptors (I 1 R) is a plasma membrane protein that is involved in diverse physiological functions. Available radioligands used so far to characterize the I 1 R were able to bind with similar affinities to ␣ 2 -adrenergic receptors (␣ 2 -ARs) and to I 1 R. This feature was a major drawback for an adequate characterization of this receptor subtype. New imidazoline analogs were therefore synthesized and the present study describes one of these compounds, 2-(2-chloro-4-iodophenylamino)-5-methyl-pyrroline (LNP 911), which was of high affinity and selectivity for the I 1 R. LNP 911 was radioiodinated and its binding properties characterized in different membrane preparations. Saturation experiments with [

G-Protein inwardly rectifying potassium channels are involved in the hypotensive effect of I1-imidazoline receptor selective ligands

“…PC12 cells were used because they express I 1 Rs but not a 2 -ARs [16] and also because most of the seminal binding studies dealing with I 1 Rs were performed in this cell line. [ 125 I]LNP911 was employed to selectively label these receptors because it is the only ligand selective for I 1 Rs available in a radioactive form [27].…”

“…LNP509 [14] and LNP911 [27] were synthesized in the Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Strasbourg, France. LNP640 [(5-bromo-quinoxalin-6-yl)-(4-methyl-4,5-dihydro-1H-imidazol-2-yl)-amine] was synthesized according to Jeon et al [28].…”

Synthesis and Biological Evaluation of 2-Aryliminopyrrolidines as Selective Ligands for I1 Imidazoline Receptors: Discovery of New Sympatho-Inhibitory Hypotensive Agents with Potential Beneficial Effects in Metabolic Syndrome

“…29,46,47 The high affinity sites are the ones involved in the biological activities of the I 1 Rs. 24,28,48,49 These are the reasons why only the high affinity sites are taken into account here.…”

Imidazoline Antihypertensive Drugs: Selective I1‐Imidazoline Receptors Activation

“…The LNP 906 and S23757 clearly antagonized the decrease in forskolin‐stimulated cAMP level induced by I 1 ‐IR agonists [68,69]. Finally, LNP 911 is not able to dose dependently decrease forskolin‐stimulated cAMP content in cells expressing only I 1 ‐imidazoline receptors, but it behaves as an allosteric enhancer [63]. The LNP 911 was radioiodinated and its binding properties characterized in different membrane preparations.…”