title: Moxonidine displays a presynaptic alpha-2-adrenoceptor-dependent synergistic sympathoinhibitory action at imidazoline-1 receptors.
abstract: The function of presynaptic imidazoline-1 receptors (I1-R) in the heart remains unclear. In rat hearts, UK14.304 and moxonidine reduced norepinephrine (NE) release. AGN192403 had no influence on NE, whereas rilmenidine, agmatine, rauwolscine, and efaroxan increased NE. These effects of moxonidine and rilmenidine were not affected by AGN192403 adminstration. Conversely, after pretreatment with UK14.304, only moxonidine displayed a pronounced inhibitory action on NE release (sensitive to AGN192403), indicating a synergistic inhibitory action at I1-R under conditions of a stimulated alpha2-adrenergic autoinhibition.
authors.affiliation: Medizinische Klinik II, Universitätsklinikum Schleswig Holstein, Lübeck, Germany. urs2001@med.cornell.edu
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schäfer
authors.forename: Christof
authors.initials: C
authors.lastname: Burgdorf
authors.forename: Astrid
authors.initials: A
authors.lastname: Engelhardt
authors.forename: Walter
authors.initials: W
authors.lastname: Raasch
authors.forename: Thomas
authors.initials: T
authors.lastname: Kurz
authors.forename: Gert
authors.initials: G
authors.lastname: Richardt
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000376:Agmatine / Q000494:pharmacology; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D004357:Drug Synergism; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006536:Heptanes / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors; D009638:Norepinephrine / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D000077769:Rilmenidine; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013565:Sympatholytics / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: C098523:AGN 192403; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001572:Benzofurans; D001643:Bridged Bicyclo Compounds; D006536:Heptanes; D007093:Imidazoles; D054755:Imidazoline Receptors; D010080:Oxazoles; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; D013565:Sympatholytics; C410887:imidazoline I1 receptors; D015016:Yohimbine; D000068438:Brimonidine Tartrate; D000376:Agmatine; C043482:moxonidine; C062597:efaroxan; D000077769:Rilmenidine; D009638:Norepinephrine