title: I(2)-imidazoline binding site affinity of a structurally different type of ligands.
abstract: Two families of compounds with affinity towards the I(2) imidazoline binding sites are reported. The first is a family of compounds structurally related to agmatine with two guanidine or 2-aminoimidazoline groups at each end of an aliphatic chain of six, eight, nine or 12 methylene groups. Second, and following the model of clonidine, we propose another family of compounds also with two guanidine or 2-aminoimidazoline groups at each end of a chain consisting of two phenyl rings connected by groups such as CH(2), CO, NH and SO(2). The affinity of the compounds towards the I(2) imidazoline binding sites was then evaluated in human brain tissues. In order to determine their pharmacological selectivity versus alpha(2)-adrenoceptors, the affinity for these receptors was also evaluated for the compounds with the highest affinities at I(2) imidazoline binding sites. The results obtained show that many of the compounds exhibit a considerable affinity towards the I(2) imidazoline binding sites. The aliphatic derivatives, in particular, present a very interesting selectivity for the I(2) imidazoline binding sites versus the alpha(2) adrenoceptors. To better understand these findings, mono-guanidinium analogues of the aliphatic derivatives were synthesised and tested showing poor affinity for I(2) imidazoline binding sites. The importance of these results lies in the novelty of the chemical structures studied (dicationic aliphatic compounds particularly) because they are significantly different to those of the I(2) imidazoline binding site ligands reported to date.
authors.affiliation: Instituto de Química Médica (CSIC), Juan de la Cierva, 3, 28006-, Madrid, Spain.
authors.forename: Christophe
authors.initials: C
authors.lastname: Dardonville
authors.forename: Isabel
authors.initials: I
authors.lastname: Rozas
authors.forename: Luis F
authors.initials: LF
authors.lastname: Callado
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Meana
mesh_terms: D001665:Binding Sites; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D054755:Imidazoline Receptors; D008024:Ligands; D011869:Radioligand Assay; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D006146:Guanidines; D007093:Imidazoles; D054755:Imidazoline Receptors; D008024:Ligands; D011955:Receptors, Drug