Bremazocine causes sympatho-inhibition and hypotension in rabbits by activating peripheral kappa-receptors.
We have studied the effects of bremazocine on the peripheral sympathetic nervous system and the arterial blood pressure of pithed rabbits with electrically (2 Hz) stimulated sympathetic outflow, and compared them with the effects of Leu-enkephalin and fentanyl. The 3H-noradrenaline plasma clearance and the plasma concentration of noradrenaline were used to calculate the rate of spillover of endogenous noradrenaline into the plasma; the spillover rate reflects the overall release of noradrenaline from postganglionic sympathetic neurones. Bremazocine (10 and 100 micrograms kg-1, followed by an infusion of 2 and 20 micrograms kg-1 h-1, respectively, i.v.) persistently decreased the noradrenaline spillover rate as well as blood pressure. Both effects were antagonized by naloxone. Leu-enkephalin (70 and 350 micrograms kg-1 min-1 i.v.) caused only transient hypotension. Fentanyl decreased blood pressure only at a very high dose (250 micrograms kg-1, followed by an infusion of 500 micrograms kg-1 h-1 i.v.). The effects of Leu-enkephalin and fentanyl were also antagonized by naloxone. When the blood pressure of pithed rabbits was raised by an intravenous infusion of noradrenaline, rather than by electrical stimulation, bremazocine, Leu-enkephalin, and fentanyl failed to produce hypotension. The results indicate that bremazocine inhibits the release of noradrenaline and, in consequence, lowers arterial pressure by activation of peripheral, probably prejunctional, opioid receptors. The receptors appear to be of the kappa-type.
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001575:Benzomorphans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003655:Decerebrate State; D004558:Electric Stimulation; D004743:Enkephalin, Leucine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D005283:Fentanyl / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood* / Q000494:pharmacology; D011817:Rabbits; D011957:Receptors, Opioid / Q000187:drug effects*; D017473:Receptors, Opioid, kappa
D000700:Analgesics; D001575:Benzomorphans; D009019:Morphinans; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D009270:Naloxone; D004743:Enkephalin, Leucine; C027248:bremazocine; D005283:Fentanyl; D009638:Norepinephrine