The effects of three kappa
opioid agonists namely,
bremazocine,
tifluadom and
U-50,488H were studied on blood pressure and heart rate in
urethane-anesthetized normal and bilateral adrenal demedullated rats.
Bremazocine (0.2, 0.4 and 0.6 mg/kg i.v.) produced a dose-dependent decrease in heart rate, while only 0.4 mg/kg
bremazocine produced marked
hypotension. The effect appeared to be long lasting because even at 60 min following
drug administration the decreases in both heart rate and blood pressure continued. Bilateral adrenal demedullation did not change
bremazocine-induced fall in blood pressure but the
bradycardia was partially blocked.
Tifluadom (0.1-0.4 mg/kg i.v.) produced an initial arrest of heart beat followed by
bradycardia which recovered in about 60 min. Except for a very transient fall soon after
drug administration no significant effect was observed on blood pressure. In adrenal demedullated rats,
tifluadom induced initial arrest of heart was not affected but the subsequent
bradycardia was blocked.
U-50,488H (0.2, 0.4 and 0.6 mg/kg i.v.) produced dose-dependent
bradycardia and
hypotension both of which were blocked following bilateral adrenal demedullation.
Naltrexone methylbromide (MRZ 2663 BR), a quaternary
opioid antagonist, injected 5 min prior to
U-50,488H, blocked its cardiovascular effects. The results suggest that kappa
opioid agonists given i.v. depress cardiovascular system and these effects are mediated through the adrenal medulla and peripheral
opioid receptors. The differential effects of kappa
opioid agonists on blood pressure and heart rate suggest that either the three kappa agents interact differentially at the
kappa opioid receptors or the subtypes of receptors for the kappa
opioid exist.