Moxonidine displays a presynaptic alpha-2-adrenoceptor-dependent synergistic sympathoinhibitory action at imidazoline-1 receptors.
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.
Schäfer
Ulrich
U
Medizinische Klinik II, Universitätsklinikum Schleswig Holstein, Lübeck, Germany. urs2001@med.cornell.edu
Burgdorf
Christof
C
Engelhardt
Astrid
A
Raasch
Walter
W
Kurz
Thomas
T
Richardt
Gert
G
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
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