Yb. Lishmanov et al., Ligands for opioid and sigma-receptors improve cardiac electrical stability in rat models of post-infarction cardiosclerosis and stress, LIFE SCI, 65(1), 1999, pp. PL13-PL17
The effects of the extremely selective mu-opioid receptor agonist, [D-Arg(2
),Lys(4)] dermorphin-(1-4)-amide (DALDA), the mu-opioid receptor agonist mo
rphine, the mu/delta agonist D-Ala(2), Leu(5), Arg-enkephalin (dalargin), t
he kappa-opioid receptor agonist spiradoline, and the sigma(1),-receptor an
tagonist DuP 734 on ventricular fibrillation threshold (VFT) was investigat
ed in an experimental post-infarction cardiosclerosis model and an immobili
zation stress-induced model in rats. Both models produced a significant dec
rease in VFT. The postinfarction cardiosclerosis-induced decrease in VFT wa
s significantly reversed by intravenous administration of dalargin (0.1 mg/
kg), DALDA (0.1 mg/kg), or morphine HCl (1.5 mg/kg). Pretreatment with nalo
xone (0.2 mg/kg) completely eliminated the increase in cardiac electrical s
tability produced by DALDA. Both spiradoline (8 mg/kg, i.p.) and DuP 734 (1
mg/kg, i.p.) produced a significant increase in VFT in rats with postinfar
ction cardiosclerosis. This effect of spiradoline was blocked by nor-binalt
orphimine. The immobilization stress-induced decrease in VFT was significan
tly reversed by administration of either DALDA, spiradoline or DuP 734. In
conclusion, activation of either mu- or kappa(1)-opioid receptors or blocka
de of sigma(1)-receptors reversed the decrease in VFT in both cardiac compr
omised models. Since DALDA and dalargin essentially do not cross blood brai
n barriers, their effects on VFT may be mediated through peripheral mu-opio
id receptors. (C) 1999 Elsevier Science Inc.