[From alpha 2-adrenergic to endazoline receptors].
Studies of the central hypotensive mode of action of the imidazolines of which clonidine is the leading molecule suggest the presence of non-catecholamine binding sites called imidazoline receptors. Our group showed that neither the endogenic ligand of alpha-adrenergic receptors, noradrenaline, nor any other tested catecholamine or phenylethylamine have hypotensive effects at the site of action of all imidazolines, the lateral reticular nucleus of the brainstem. In addition, a population of membrane binding sites which take up labelled clonidine and which are insensitive to noradrenaline have been demonstrated in the lateral reticular nucleus. An endogenic non-catecholamine substance whose structure is currently under identification and which is recognised by these receptors has been isolated from the brain tissues of various mammals. All this experimental evidence supports the hypothesis that the hypotensive effects of imidazoline-like substances are related to their action on brainstem receptors specific to this endogenic ligand which we propose to call endazoline. Rilmenidine, which has a chemical structure similar to that of the imidazolines, has a higher relative selectivity for the imidazoline binding sites than the reference molecule (clonidine). A central antihypertensive agent without the classical sedative effects associated with this class of drug could result. A study of the structure-activity relationship is needed to confirm this hypothesis.
Bousquet
P
P
Laboratoire de pharmacologie cardio-vasculaire et rénale, CNRS UA 589, faculté de médecine, université Louis-Pasteur, Strasbourg, France.
Feldman
J
J
Tibirica
E
E
Bricca
G
G
Molines
A
A
Dontenwill
M
M
Belcourt
A
A
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D054755:Imidazoline Receptors; D010080:Oxazoles / Q000627:therapeutic use*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011955:Receptors, Drug / Q000502:physiology; D000077769:Rilmenidine
D000959:Antihypertensive Agents; D054755:Imidazoline Receptors; D010080:Oxazoles; D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug; D000077769:Rilmenidine
Des récepteurs alpha 2-adrénergiques aux récepteurs à l'endazoline.