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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1971 Sep;43(1):53–66. doi: 10.1111/j.1476-5381.1971.tb07156.x

Effects of narcotic analgesics and antagonists on the in vivo release of acetylcholine from the cerebral cortex of the cat

K Jhamandas, J W Phillis, C Pinsky
PMCID: PMC1665943  PMID: 5136464

Abstract

1. In cats under light allobarbitone anaesthesia, the effects of intravenous injections of narcotic and non-narcotic analgesics, of a general depressant, and of narcotic antagonists were investigated on the spontaneous release of acetylcholine (ACh) from the surface of the sensorimotor cortex.

2. The narcotic analgesics morphine (0·1, 1·0 and 5 mg/kg), meperidine (1·0 and 2·0 mg/kg), methadone (1·0 mg/kg) and codeine (5·0 and 10·0 mg/kg) greatly reduced ACh release.

3. The non-narcotic analgesics pentazocine (1·0 and 2·0 mg/kg) and propoxyphene (5·0 and 10·0 mg/kg) as well as the depressant chlorpromazine (0·25, 0·5 and 1·0 mg/kg) also greatly reduced ACh release.

4. Two of the three narcotic antagonists examined, levallorphan (0·1, 1·0 and 5 mg/kg) and nalorphine (1·0 mg/kg) had the property of reducing ACh release. They were thus partial agonists. With levallorphan the greatest reduction occurred with the smallest dose injected and the effect was regularly obtained, whereas with nalorphine a reduction was obtained in some experiments only. The third, naloxone, was a specific narcotic antagonist and did not reduce the ACh release in any dose (0·01, 0·1, 0·5 and 1·0 mg/kg) examined. In a dose of 1·0 mg/kg it actually produced a small increase in Ach release.

5. Naloxone (0·1-1·0 mg/kg) restored the reduction in ACh release produced by the narcotic analgesics and by the partial agonist levallorphan. It partially restored the reduction produced by the non-narcotic analgesics and by nalorphine, but had no effect on the reduction produced by chlorpromazine.

6. The relevance of these results with regard to analgesia and to the narcotic abstinence syndrome is discussed.

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Selected References

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

  1. BELESLIN D., POLAK R. L. DEPRESSION BY MORPHINE AND CHLORALOSE OF ACETYLCHOLINE RELEASE FROM THE CAT'S BRAIN. J Physiol. 1965 Apr;177:411–419. doi: 10.1113/jphysiol.1965.sp007600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. CHAPMAN J. E., WALASZEK E. J. Antagonism of some toxic effects of destropropoxyphene by nalorphine. Toxicol Appl Pharmacol. 1962 Nov;4:752–758. doi: 10.1016/0041-008x(62)90105-9. [DOI] [PubMed] [Google Scholar]
  3. Cox B. M., Weinstock M. The effect of analgesic drugs on the release of acetylcholine from electrically stimulated guinea-pig ileum. Br J Pharmacol Chemother. 1966 May;27(1):81–92. doi: 10.1111/j.1476-5381.1966.tb01643.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Crossland J., Slater P. The effect of some drugs on the "free" and "bound" acetylcholine content of rat brain. Br J Pharmacol Chemother. 1968 May;33(1):42–47. doi: 10.1111/j.1476-5381.1968.tb00472.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. FRIEDGOOD C. E., RIPSTEIN C. B. Use of chlorpromazine in the withdrawal of addicting drugs; preliminary report. N Engl J Med. 1955 Feb 10;252(6):230–233. doi: 10.1056/NEJM195502102520607. [DOI] [PubMed] [Google Scholar]
  6. Fraser H. F. Propoxyphene antidotes. JAMA. 1968 May 6;204(6):549–549. [PubMed] [Google Scholar]
  7. Frederickson R. C., Pinsky C. Morphine impairs acetylcholine release but facilitates acetylcholine action at a skeletal neuromuscular junction. Nat New Biol. 1971 May 19;231(20):93–94. doi: 10.1038/newbio231093a0. [DOI] [PubMed] [Google Scholar]
  8. Gary N. E., Maher J. F., DeMyttenaere M. H., Liggero S. H., Scott K. G., Matusiak W., Schreiner G. E. Acute propoxyphene hydrochloride intoxication. Arch Intern Med. 1968 May;121(5):453–457. [PubMed] [Google Scholar]
  9. Gyand E. A., Kosterlitz H. W. Agonist and antagonist actions of morphine-like drugs on the guinea-pig isolated ileum. Br J Pharmacol Chemother. 1966 Sep;27(3):514–527. doi: 10.1111/j.1476-5381.1966.tb01864.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. HANO K., KANETO H., KAKUNAGA T., MORIBAYASHI N. PHARMACOLOGICAL STUDIES OF ANALGESICS--VI. THE ADMINISTRATION OF MORPHINE AND CHANGES IN ACETYLCHOLINE METABOLISM MOUSE BRAIN. Biochem Pharmacol. 1964 Mar;13:441–447. doi: 10.1016/0006-2952(64)90164-9. [DOI] [PubMed] [Google Scholar]
  11. Howes J. F., Harris L. S., Dewey W. L. The effect of morphine, nalorphine, naloxone, pentazocine, cyclazocine and oxotremorine on the synthesis and release of acetylcholine by mouse cerebral cortex slices in vitro. Arch Int Pharmacodyn Ther. 1970 Apr;184(2):267–276. [PubMed] [Google Scholar]
  12. Howes J. F., Harris L. S., Dewey W. L., Voyda C. A. Brain acetylcholine levels and inhibition of the tail-flick reflex in mice. J Pharmacol Exp Ther. 1969 Sep;169(1):23–28. [PubMed] [Google Scholar]
  13. Jhamandas K., Pinsky C., Phillis J. W. Effects of morphine and its antagonists on release of cerebral cortical acetylcholine. Nature. 1970 Oct 10;228(5267):176–177. doi: 10.1038/228176a0. [DOI] [PubMed] [Google Scholar]
  14. Kallos T., Smith T. G. Naloxone reversal of pentazocine-induced respiratory depression. JAMA. 1968 Jun 3;204(10):932–932. [PubMed] [Google Scholar]
  15. Kosterlitz H. W., Watt A. J. Kinetic parameters of narcotic agonists and antagonists, with particular reference to N-allylnoroxymorphone (naloxone). Br J Pharmacol Chemother. 1968 Jun;33(2):266–276. doi: 10.1111/j.1476-5381.1968.tb00988.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Large W. A., Milton A. S. The effect of acute and chronic morphine administration on brain acetylcholine levels in the rat. Br J Pharmacol. 1970 Feb;38(2):451P–452P. [PMC free article] [PubMed] [Google Scholar]
  17. Mitchell J. F. The spontaneous and evoked release of acetylcholine from the cerebral cortex. J Physiol. 1963 Jan;165(1):98–116. doi: 10.1113/jphysiol.1963.sp007045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. PATON W. D. The action of morphine and related substances on contraction and on acetylcholine output of coaxially stimulated guinea-pig ileum. Br J Pharmacol Chemother. 1957 Mar;12(1):119–127. doi: 10.1111/j.1476-5381.1957.tb01373.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. PELIKAN E. W. The mechanism of ganglionic blockade produced by nicotine. Ann N Y Acad Sci. 1960 Sep 27;90:52–69. doi: 10.1111/j.1749-6632.1960.tb32617.x. [DOI] [PubMed] [Google Scholar]
  20. Phillis J. W. Acetylcholine release from the cerebral cortex: its role in cortical arousal. Brain Res. 1968 Mar;7(3):378–389. doi: 10.1016/0006-8993(68)90004-8. [DOI] [PubMed] [Google Scholar]
  21. SCHAUMANN W. Inhibition by morphine of the release of acetylcholine from the intestine of the guinea-pig. Br J Pharmacol Chemother. 1957 Mar;12(1):115–118. doi: 10.1111/j.1476-5381.1957.tb01372.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sharkawi M., Schulman M. P. Inhibition by morphine of the release of [14c]acetylcholine from rat brain cortex slices. J Pharm Pharmacol. 1969 Aug;21(8):546–547. doi: 10.1111/j.2042-7158.1969.tb08311.x. [DOI] [PubMed] [Google Scholar]
  23. Shute C. C., Lewis P. R. The ascending cholinergic reticular system: neocortical, olfactory and subcortical projections. Brain. 1967 Sep;90(3):497–520. doi: 10.1093/brain/90.3.497. [DOI] [PubMed] [Google Scholar]
  24. Silvestrini B., Quadri E. Investigations on the specificity of the so-called analgesic activity of non-narcotic drugs. Eur J Pharmacol. 1970 Oct;12(2):231–235. doi: 10.1016/0014-2999(70)90069-5. [DOI] [PubMed] [Google Scholar]
  25. Zelson C., Kahn E. J., Neumann L., Polk G. Heroin withdrawal syndrome. J Pediatr. 1970 Mar;76(3):483–484. doi: 10.1016/s0022-3476(70)80498-x. [DOI] [PubMed] [Google Scholar]

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