[The anti-arrhythmia and pro-arrhythmia properties of sigma-receptor ligands].
It has been found that the sigma 1- and sigma 3-receptor antagonists, DuP 734 intraperitoneally and XJ 448 intravenously, had antiarrhythmic effects against epinephrine-induced arrhythmias in rats. The ED50 for antiarrhythmic effect of DuP 734 was 0.157 mg/kg after intraperitoneal administration. Other sigma-receptor antagonists (rimcazole, BMY 14802, haloperidol) did not affect the incidence of epinephrine-induced arrhythmias. sigma 1-Receptor agonists (DTG, N-allyl-normetazocine, (+)-3-PPP, (-)-3-PPP) had proarrhythmic effect after systemic administration. The sigma-agonist N-allyl-normetazocine and sigma-antagonist XJ 488 had no effect on the incidence of epinephrine-induced arrhythmias after intracerebroventricular administration. Therefore, it appears that the central nervous system does not play a significant role in the antiarrhythmic or proarrhythmic effects of sigma ligands. We hypothesize that these effects of sigma ligands might be dependent on their action on cardiac sigma receptors.
Lishmanov
Iu B
IuB
Department of Experimental Cardiology, Tomsk Scientific Center, Siberian Division, Russian Academy of Medical Sciences, Russia.
Maslov
L N
LN
Krylatov
A V
AV
Ugdyzhekova
D S
DS
Gilligan
P
P
Tam
S W
SW
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine; D008024:Ligands; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D008024:Ligands; D017480:Receptors, sigma; D004837:Epinephrine