Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1973 Dec;49(4):628–641. doi: 10.1111/j.1476-5381.1973.tb08538.x

Effects of narcotic analgesics and their antagonists on the rabbit isolated heart and its adrenergic nerves

H Montel, K Starke
PMCID: PMC1776589  PMID: 4788036

Abstract

1. In isolated perfused hearts of rabbits, the effects of morphine, methadone, pethidine, fentanyl, levallorphan and naloxone on heart rate, the spontaneous outflow of noradrenaline, the uptake of infused noradrenaline and the overflow of noradrenaline in response to stimulation of the accelerans nerves were investigated.

2. At concentrations of 10-100 μM, methadone, fentanyl, levallorphan and naloxone, but not morphine and pethidine, decreased the heart rate. Only pethidine and levallorphan (100 μM) augmented the spontaneous outflow of noradrenaline.

3. With the exception of naloxone, all drugs diminished the neuronal uptake of noradrenaline from the perfusion fluid. Methadone and pethidine (1 μM) were the most effective inhibitors. The inhibitory effect of morphine was not antagonized by naloxone.

4. All drugs increased the overflow of noradrenaline evoked by stimulation of the accelerans nerves at 5 Hz. Simultaneously, the positive chronotropic effect of stimulation was usually enhanced. Morphine also augmented the response to stimulation at 2·5 and 10 Hz. The effect of morphine was prevented by pre-infusion of cocaine. The response to stimulation was never depressed.

5. It is concluded that the adrenergic nerves of the rabbit heart lack specific morphine receptors which in some other sympathetic nerves mediate an inhibition of the stimulation-induced secretion of noradrenaline. The mechanism of the enhancement of adrenergic neurotransmission by relatively high concentrations of the drugs is discussed.

Full text

PDF
628

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. CAIRNIE A. B., KOSTERLITZ H. W., TAYLOR D. W. Effect of morphine on some sympathetically innervated effectors. Br J Pharmacol Chemother. 1961 Dec;17:539–551. doi: 10.1111/j.1476-5381.1961.tb01141.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ciofalo F. R. Effects of some narcotics and antagonists on synaptosomal 3 H-norepinephrine uptake. Life Sci I. 1972 Jun 15;11(12):573–580. doi: 10.1016/0024-3205(72)90192-0. [DOI] [PubMed] [Google Scholar]
  3. GYANG E. A., KOSTERLITZ H. W., LEES G. M. THE INHIBITION OF AUTONOMIC NEURO-EFFECTOR TRANSMISSION BY MORPHINE-LIKE DRUGS AND ITS USE AS A SCREENING TEST FOR NARCOTIC ANALGESIC DRUGS . Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1964 May 25;248:231–246. doi: 10.1007/BF00348594. [DOI] [PubMed] [Google Scholar]
  4. Henderson G., Hughes J., Kosterlitz H. W. A new example of a morphine-sensitive neuro-effector junction: adrenergic transmission in the mouse vas deferens. Br J Pharmacol. 1972 Dec;46(4):764–766. doi: 10.1111/j.1476-5381.1972.tb06901.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Henderson G., Hughes J., Thompson J. W. The variation of noradrenaline output with frequency of nerve stimulation and the effect of morphine on the cat nictitating membrane and on the guinea-pig myenteric plexus. Br J Pharmacol. 1972 Nov;46(3):524P–525P. [PMC free article] [PubMed] [Google Scholar]
  6. Inturrisi C. E., Verebely K. The levels of methadone in the plasma in methadone maintenance. Clin Pharmacol Ther. 1972 Sep-Oct;13(5):633–637. doi: 10.1002/cpt1972135part1633. [DOI] [PubMed] [Google Scholar]
  7. Kennedy B. L., West T. C. Effect of morphine on electrically-induced release of autonomic mediators in the rabbit sinoatrial node. J Pharmacol Exp Ther. 1967 Jul;157(1):149–158. [PubMed] [Google Scholar]
  8. LINDMAR R., MUSCHOLL E. DIE WIRKUNG VON PHARMAKA AUF DIE ELIMINATION VON NORADRENALIN AUS DER PERFUSIONSFLUESSIGKEIT UND DIE NORADRENALINEUFNAHME IN DAS ISOLIERTE HERZ. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1964 Jul 28;247:469–492. doi: 10.1007/BF00329896. [DOI] [PubMed] [Google Scholar]
  9. PALMER J. F. THE USE OF B-THIOPROPIONIC ACID FOR THE ANALYSIS OF MIXTURES OF ADRENALINE AND NORADRENALINE IN PLASMA BY THE FLUOROMETRIC TRIHYDROXYINDOLE METHOD. West Indian Med J. 1964 Mar;13:38–53. [PubMed] [Google Scholar]
  10. SZERB J. C. The effect of morphine on the adrenergic nerves of the isolated guinea-pig jejunum. Br J Pharmacol Chemother. 1961 Feb;16:23–31. doi: 10.1111/j.1476-5381.1961.tb00294.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Starke K. Action of angiotensin on uptake, release and metabolism of 14C-noradrenaline by isolated rabbit hearts. Eur J Pharmacol. 1971 Apr;14(2):112–123. doi: 10.1016/0014-2999(71)90204-4. [DOI] [PubMed] [Google Scholar]
  12. TRENDELENBURG U. The action of morphine on the superior cervical ganglion and on the nictitating membrane of the cat. Br J Pharmacol Chemother. 1957 Mar;12(1):79–85. doi: 10.1111/j.1476-5381.1957.tb01366.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Trendelenburg U. The effect of cocaine on the pacemaker of isolated guinea-pig atria. J Pharmacol Exp Ther. 1968 Jun;161(2):222–231. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES