title: Historic aspects in the identification of the I1 receptor and the pharmacology of imidazolines.
abstract: The central nervous system is involved in the control of arterial blood pressure. Stimulation of central alpha 2-adrenoceptors in the nucleus tractus solitarii (NTS) decreases sympathetic outflow, resulting in a fall in arterial blood pressure. One of the first antihypertensive substances with actions on the alpha 2-adrenoceptors of the NTS was alpha-methylnoradrenaline. Later on the imidazoline clonidine was developed for which numerous effects, mediated by alpha 2-adrenoceptors, in the CNS could be demonstrated. Since the centrally acting alpha 2-adrenoceptor agonists possess severe side effects, the development of more specific and selective centrally acting imidazolines resulted in the derivatives moxonidine and rilmenidine. The effects of the "second-generation imidazolines" could not be fully understood as alpha 2-adrenoceptor agonists. In the meantime, the rostral ventrolateral medulla (RVLM) has been identified as the site of action of the imidazolines and an I1-imidazoline binding site was characterized in this region. For the antihypertensive action of the imidazolines, agonism at the I1-imidazoline subtype seems to be responsible. In addition, an acid- and heat-stable endogenous substance, called clonidine displacing substance (CDS), was reported to bind at the putative I receptor. In 1992 a receptor protein for I receptors (70 kD) could be separated that is different from that of alpha 2-adrenoceptors. However, up to now we are still lacking the amino-acid sequence of the I receptor and its second messenger system.
authors.affiliation: Institute of Pharmacology, Medical University of Lübeck, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Dominiak
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D054755:Imidazoline Receptors; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D011955:Receptors, Drug / Q000187:drug effects* / Q000502:physiology
chemical_list: D000959:Antihypertensive Agents; D007093:Imidazoles; D054755:Imidazoline Receptors; D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug