[Specificity of the anti-arrhythmic effect of kappa1-opioid receptor agonists].
It is demonstrated that intravenous administration of the kappa 1-opioid receptor (OR) agonists (-)-trans-(1S,S)-U-50,488 and (+)-trans-(1R,2R)-U-50,488 increases heart tolerance to the arrhythmogenic effect of epinephrine in rats. This antiarrhythmic effect was completely abolished by preliminary kappa-OR blocking with norbinaltorphimine. Preliminary administration of of a high-affinity kappa 1-OR agonist (-)-trans-(1S,S)-U-50,488 significantly reduced the incidence of ventricular arrhythmias upon coronary artery occlusion and reperfusion in vivo. The low-affinity (+)-trans-(1R,2R)-U-50,488 does not show antiarrhythmic activity under ischemia and reperfusion of myocardium. It is concluded that the antiarrhythmic action of kappa 1-OR agonists in the adrenal, ischemic, and reperfusion arrhythmia models has a receptor-specific character.
Ugdyzhekova
D S
DS
Laboratory of Experimental Cardiology, Institute of Cardiology, Tomsk Scientific Center, Siberian Division, Russian Academy of Medical Sciences, ul. Kievskaya 111, Tomsk, 634050 Russia.
Maslov
L N
LN
Krylatov
A V
AV
Lishmanov
Iu B
IuB
Tam
S V
SV
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D004562:Electrocardiography; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000889:Anti-Arrhythmia Agents; D017473:Receptors, Opioid, kappa; C116587:kappa(1) opioid receptor; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer