Skip to main content
SpringerLink
Log in

New and Experimental Therapeutic Roles for Naloxone and Related Opioid Antagonists

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Summary

Naloxone and related opioid antagonists have been shown to have therapeutic utility in a variety of conditions. The effects of opioid antagonists in either physiological or pathological processes are most clearly seen when there is excessive occupancy of opioid receptors, as in opiate overdose. Opioid antagonists are also able to reverse several types of cardiovascular shock, conditions in which endogenous opioids appear to be mobilised, resulting in increased opioid receptor occupation. There are also more controversial circumstances in which excessive occupation of opioid receptors may assume pathological significance, such as hypercapnia. Opioid antagonists could be useful in such a situation by re-sensitising the respiratory centres to carbon dioxide.

There is some evidence that opioid antagonists may benefit some schizophrenic and manic-depressive patients, suggesting that an endogenous opioid ligand might cause disturbances in mental functioning. The diversity and complexity of opioid mechanisms in the central nervous system suggest that more specific opioid antagonists could be more selective in altering physiological or pathological functioning.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Akil, H.; Mayer D.J. and Liebeskind, J.C.: Antagonism of stimulation produced analgesia by naloxone, a narcotic antagonist. Science 191: 961–962 (1976).

    PubMed  CAS  Google Scholar 

  • Akil, H.; Watson, S.J.; Berger, P.A. and Barchas, J.D.: Endorphins. β-LPH, and ACTH: Biochemical, pharmacological and anatomical studies; in Costa and Trabucchi (Eds) Advances in Biochemical Psychopharmacology 18: 125–139 (Raven Press, New York 1978).

    PubMed  CAS  Google Scholar 

  • Baskin, D.S. and Hosobuchi, Y.: Naloxone reversal of ischaemic neurological deficits in man. Lancet 2: 272–275 (1981).

    PubMed  CAS  Google Scholar 

  • Baskin, D.S.; Kieck, C.F. and Hosobuchi, Y.: Naloxone reversal of ischemic neurologic deficits in baboons is not mediated by systemic effects. Life Sciences 31: 2201–2204 (1982).

    PubMed  CAS  Google Scholar 

  • Bell, E.F.: The use of naloxone in the treatment of diazepam poisoning. Journal of Pediatrics 87: 803–804 (1975).

    PubMed  CAS  Google Scholar 

  • Bennett, P.B.: Naloxone fails to antagonize the righting response in rats anesthetized with halothane. Anesthesiology 49: 9–11 (1978).

    PubMed  CAS  Google Scholar 

  • Berger, P.A.; Watson, S.J.; Akil, H. and Barchas, J.D.: Naloxone administration in chronic hallucinating schizophrenic patients; in Usden et al. (Eds) Endorphins in Mental Health Research, pp.423–434 (Oxford University Press, New York 1979).

    Google Scholar 

  • Berkowitz, B.A.; Finck, A.D. and Ngai, S.H.: Nitrous oxide analgesia: Reversal by naloxone and development of tolerance. Journal of Pharmacology and Experimental Therapeutics 203: 539–547 (1977).

    PubMed  CAS  Google Scholar 

  • Beubler, E.: Naloxone increases carbon dioxide stimulated respiration in the rabbit. Naunyn-Schmiedeberg’s Archives of Pharmacology 311: 199–203 (1980).

    PubMed  CAS  Google Scholar 

  • Billingsley, M.L. and Kubena, A.K.: Effects of naloxone and Picrotoxin on the sedative and anticonflict effects of benzodiazepines. Life Sciences 22: 897–906 (1978).

    PubMed  CAS  Google Scholar 

  • Billingsley, M.; Suria, A. and Williams, J.: Effects of Picrotoxin, naloxone, and vagotomy on chlordiazepoxide-induced respiratory depression. Archives Internationales de Pharmacodynamic et de Thérapie 242: 95–103 (1979).

    CAS  Google Scholar 

  • Blumberg, H. and Dayton, H.B.: Naloxone, naltrexone and related noroxymorphones; in Braude et al. (Eds), Narcotic Antagonists, pp.33–43 (Raven Press, New York 1974).

    Google Scholar 

  • Blumberg, H.; Dayton, H.B.; George, M. and Rapaport, D.N.: N-allylnoroxymorphone: A potent narcotic antagonist. Federation Proceedings 20: 311 (1961).

    Google Scholar 

  • Bolme, P.; Fuxe, K.; Bradley, A.R. and Smythee, J.: Cardiovascular effects of morphine and opioid peptides following intracisternal administration in chloralose-anesthetized rats. European Journal of Pharmacology 48: 319–324 (1978).

    PubMed  CAS  Google Scholar 

  • Borison, H.L.: Central nervous respiratory depressants — Narcotic analgesics. Pharmacology and Therapeutics B 3: 227–237 (1977).

    CAS  Google Scholar 

  • Butland, R.J.A.; Woodcock, A.A.; Gross, E.R. and Geddes, D.M.: Endogenous opioids (endorphins) and the control of breathing. New England Journal of Medicine 305: 1096 (1981).

    PubMed  CAS  Google Scholar 

  • Catley, D.M.; Jordan, C.; Frith, C.A.; Lehane, J.R.; Rhodes, A.M. and Jones, J.G.: Alcohol induced discoordination is not reversed by naloxone. Psychopharmacology 75: 65–68 (1981a).

    PubMed  CAS  Google Scholar 

  • Catley, D.M.; Lehane, J.R. and Jones, J.G.: Failure of naloxone to reverse alcohol intoxication. Lancet 1: 1263 (1981b).

    PubMed  CAS  Google Scholar 

  • Chang, K.-J. and Cuatrecasas, P.: Heterogeneity and properties of opiate receptors. Federation Proceedings 40: 2729–2734 (1981).

    PubMed  CAS  Google Scholar 

  • Christensen, K.N. and Hüttel, M.: Naloxone does not antagonize diazepam-induced sedation. Anesthesiology 51: 187 (1979).

    PubMed  CAS  Google Scholar 

  • Davis, G.C.; Bunney, W.E. Jr; DeFraites, E.G.; Kleinman, J.E.; van Kammen, D.P.; Post, R.M. and Wyatt, R.J.: Intravenous naloxone administration in schizophrenia and affective illness. Science 197: 74–77 (1977).

    PubMed  CAS  Google Scholar 

  • Dayton, H.B. and Blumberg, H.: The use of the narcotic antagonist naloxone with barbiturate-narcotic combinations in rats. Federation Proceedings 31: 507 (1972).

    Google Scholar 

  • Denavit-Saubié, M.; Champagnat, J. and Zieglgänsberger, W.: Effects of opiates and methionine-enkephalin on pontine and bulbar respiratory neurons of the cat. Brain Research 155: 55–67 (1978).

    PubMed  Google Scholar 

  • Dirksen, R.; Otten, M.H.; Wood, G.J.; Verbaan, C.J.; Haalebos, M.M.P.; Verdouw, P.V. and Nejhuis, G.M.M.: Naloxone in shock (correspondence). Lancet 2: 1360–1361 (1980).

    Google Scholar 

  • Drysdale, A.; Deacon, R,; Lewis, P.; Olley, J.; Electricwala, A. and Sherwood R.: A peptide-containing fraction of plasma from schizophrenic patients which binds to opiate receptors and induces hyper-reactivity in rats. Neuroscience 7: 1557–1563 (1980).

    Google Scholar 

  • Duncalf, D.; Nagashima, H. and Duncalf, R.M.: Naloxone fails to antagonize thiopental anesthesia. Anesthesia and Analgesia 57: 558–562 (1978).

    PubMed  CAS  Google Scholar 

  • Eckenhoff, J.E.; Elder, J.D. and King, B.D.: Effect of N-allylnor-morphine in treatment of opiate overdose. American Journal of Medical Science 222: 115–117 (1951).

    Google Scholar 

  • Emrich, H.M.; Cording, C; Pirée, S.; Kölling, A.; Möller, H.-J.; von Zerssen, D. and Herz, A.: Actions of naloxone in different types of psychoses; in Usdin et al. (Eds), Endorphins in Mental Health Research, pp.452–460 (Oxford University Press, New York 1979).

    Google Scholar 

  • Emrich, H.M.; Cording, C; Pirée, S.; Kölling, A.; Zerssen, D.V. and Herz, A.: Indication of an antipsychotic action of the opiate antagonist naloxone. Pharmakopsychiatrie 10: 265–270 (1977).

    CAS  Google Scholar 

  • Faden, A.I. and Holaday, J.W.: Opiate antagonists: A role in the treatment of hypovolemic shock. Science 205: 317–318 (1979).

    PubMed  CAS  Google Scholar 

  • Faden, A.I. and Holaday, J.W.: Naloxone treatment of endotoxin shock: Stereospecificity of physiologic and pharmacologic effects in the rat. Journal of Pharmacology and Experimental Therapeutics 212: 441–447 (1980).

    PubMed  CAS  Google Scholar 

  • Faden, A.I.; Jacobs, T.P. and Holaday, J.W.: Endorphin-parasympathetic interaction in spinal shock. Journal of the Autonomic Nervous System 2: 295–304 (1980).

    PubMed  CAS  Google Scholar 

  • Faden, A.I.; Jacobs, T.P. and Holaday, J.W.: Opiate antagonist improves neurologic recovery after spinal injury. Science 211: 493–494 (1981).

    PubMed  CAS  Google Scholar 

  • Feuerstein, G.; Chiueh, C.C. and Kopin, I.J.: Effect of naloxone on the cardiovascular and sympathetic response to hypovolemic hypotension in the rat. European Journal of Pharmacology 75: 65–69 (1981).

    PubMed  CAS  Google Scholar 

  • Finck, A.D.; Ngai, S.H. and Berkowitz, B.A.: Antagonism of general anesthesia by naloxone in the rat. Anesthesiology 44: 241–245 (1977).

    Google Scholar 

  • Fleetham, J.A.; Clarke, H.; Dhingra, S.; Chernick, V. and Anthonisen, N.R.: Endogenous opiates and chemical control of breathing in humans. American Review of Respiratory Disease 121: 1045–1049 (1980).

    PubMed  CAS  Google Scholar 

  • Flórez, J. and Mediavilla, A.: Respiratory and cardiovascular effects of metenkephalin applied to the ventral surface of the brain stem. Brain Research 138: 585–590 (1977).

    PubMed  Google Scholar 

  • Flórez, J.; Mediavilla, A. and Pazos, A.: Respiratory effects of β-endorphin, D-ala2-met-enkephalinamide, and met-enkephalin injected into the lateral ventricle and the pontomedullary subarachnoid space. Brain Research 199: 197–206 (1980).

    PubMed  Google Scholar 

  • Flórez, J.; Hurlé, M.A. and Mediavilla, A.: Respiratory responses to opiates applied to the medullary ventral surface. Life Sciences 31: 2189–2192 (1982).

    PubMed  Google Scholar 

  • Foldes, F.F.; Lunn, J.N.; Moore, J. and Brown, I.M.: N-Allyl-noroxymorphone: A new potent narcotic antagonist. American Journal of Medical Sciences 245: 23–30 (1963).

    CAS  Google Scholar 

  • Freye, E. and Arndt, J.O.: Perfusion of the fourth cerebral ventricle with fentanyl induces naloxone-reversible bradycardia, hypotension, and EEG synchronization in conscious dogs. Naunyn-Schmiedeberg’s Archives of Pharmacology 307: 123–128 (1979).

    PubMed  CAS  Google Scholar 

  • Freye, E. and Hartung, E.: Fentanyl in the fourth cerebral ventricle causes respiratory depression in the anesthetized but not in the awake dog. Acta Anaesthesiologica Scandinavica 25: 171–173 (1981).

    PubMed  CAS  Google Scholar 

  • Freye, E.; Hartung, E. and Schenk, G.K.: Perfusion of the fourth cerebral ventricle with the synthetic opioid peptide, FK 33-824, induces dose related bradycardia and naloxone-reversible respiratory depression in the awake dog. Pharmacology 25: 6–11 (1982).

    PubMed  CAS  Google Scholar 

  • Fürst, Z.; Foldes, F.F. and Knoll, J.: The influence of naloxone on barbiturate anesthesia and toxicity in the rat. Life Sciences 20: 921–926 (1977).

    PubMed  Google Scholar 

  • Gilbert, P.E. and Martin, W.R.: Antagonism of the effects of pentobarbital in the chronic spinal dog by naltrexone. Life Sciences 20: 1401–1406 (1977).

    PubMed  CAS  Google Scholar 

  • Gitlin, M. and Rosenblatt, M.: Possible withdrawal from endogenous opiates in schizophrenics. American Journal of Psychiatry 135: 377–378 (1978).

    PubMed  CAS  Google Scholar 

  • Gritz, E.R.; Shiffman, S.M.; Jarvik, M.E.; Schlesinger, J. and Charuvastra, V.C.: Naltrexone; Physiological and psychological effects of single doses. Clinical Pharmacology and Therapeutics 19: 773–776 (1976).

    PubMed  CAS  Google Scholar 

  • Gunne, L.-M.; Lindström, L. and Terenius, L.: Naloxone-induced reversal of schizophrenic hallucinations. Journal of Neural Transmission 40: 13–19 (1977).

    PubMed  CAS  Google Scholar 

  • Haertzen, C.A.: Subjective effects of narcotic antagonists; in Braude et al. (Eds) Narcotic Antagonist. Advances in Biochemical Psychopharmacology, Vol. 8, pp.383–398 (Raven Press, New York 1974).

    Google Scholar 

  • Harper, M.H.; Winter, P.M.; Johnson, B.H. and Eger, E.I. Jr: Naloxone does not antagonize general anesthesia in the rat. Anesthesiology 49: 3–5 (1978).

    PubMed  CAS  Google Scholar 

  • Hart, E.R. and McCawley, E.L.: The pharmacology of N-allyl-normorphine as compared with morphine. Journal of Pharmacology and Experimental Therapeutics 82: 339–348 (1944).

    CAS  Google Scholar 

  • Holaday, J.W. and Faden, A.I.: Naloxone reversal of endotoxin hypotension suggests role of endorphins in shock. Nature 275: 450–451 (1978).

    PubMed  CAS  Google Scholar 

  • Holaday, J.W. and Faden, A.I.: Naloxone acts at central opiate receptors to reverse hypotension, hypothermia and hypoventilation in spinal shock. Brain Research 189: 295–299 (1980).

    PubMed  CAS  Google Scholar 

  • Holaday, J.W. and Faden, A.I.: Naloxone reverses the pathophysiology of shock through an antagonism of endorphin systems; in Martin et al. (Eds), Neurosecretion and Brain Peptides, pp.421–434 (Raven Press, New York 1981).

    Google Scholar 

  • Hosobuchi, Y.; Baskin, D.S. and Woo, S.K.: Reversal of induced ischemic neurologic deficit in gerbils by the opiate antagonist naloxone. Science 215: 69–71 (1982).

    PubMed  CAS  Google Scholar 

  • Isbell, H. and Fraser, H.F.: Addiction to analgesics and barbiturates. Pharmacological Reviews 2: 355–397 (1950).

    Google Scholar 

  • Iselin, H.U.; Weiss, P.; Gonzalez-Miranda, F.; Gillman, M.A. and Lichfield, F.J.: Naloxone reversal of ischaemic neurological deficits. Lancet 2: 642 (1981).

    Google Scholar 

  • Isom, G.E. and Elshowihy, R.M.: Naloxone-induced enhancement of carbon dioxide stimulated respiration. Life Sciences 31: 113–118 (1982).

    PubMed  CAS  Google Scholar 

  • Iwamoto, E.T.: Locomotor activity and antinociception after putative mu, kappa and sigma opioid receptor agonists in the rat: Influence of dopaminergic agonists and antagonists. Journal of Pharmacology and Experimental Therapeutics 217: 451–460 (1981).

    PubMed  CAS  Google Scholar 

  • Janowsky, D.S.; Segal, D.S.; Bloom, F.; Abrams, A. and Guillemin, R.: Lack of effect of naloxone on schizophrenic subjects. American Journal of Psychiatry 134: 926–927 (1977).

    PubMed  CAS  Google Scholar 

  • Jasinski, D.R.; Martin, W.R. and Haertzen, C.A.: The human pharmacology and abuse potential of N-allylnoroxymorphone (naloxone). Journal of Pharmacology and Experimental Therapeutics 157: 420–426 (1967).

    PubMed  CAS  Google Scholar 

  • Jasinski, D.R.; Martin, W.R. and Sapira, J.D.: Antagonism of the subjective, behavioral, pupillary, and respiratory depressant effects of cyclazocine by naloxone. Clinical Pharmacology and Therapeutics 9: 215–222 (1968).

    PubMed  CAS  Google Scholar 

  • Jasinski, D.R.; Shannon, H.E.; Cone, E.J.; Vaupel, D.B.; Risner, M.E.; McQuinn, R.L.; Su, T.-P. and Pickworth, W.B.: Interdisciplinary studies on phencyclidine; in Domino (Ed.), PCP (Phencyclidine): Historical and Current Perspectives, pp.331–400 (NPP Books, Ann Arbor 1981).

    Google Scholar 

  • Jeffcoate, W.J.; Cullen, M.H.; Herbert, M.; Hastings, A.G. and Walder, C.P.: Prevention of effects of alcohol intoxication by naloxone. Lancet 2: 1157–1159 (1979).

    PubMed  CAS  Google Scholar 

  • Jefferys, D.B.; Flanagan, R.J. and Volans, G.N.: Reversal of ethanol-induced coma with naloxone. Lancet 1: 308–309 (1980).

    PubMed  CAS  Google Scholar 

  • Johnstone, R.E.; Jobes, D.R.; Kenneil, E.M.; Behar, M.G. and Smith, T.C.: Reversal of morphine anesthesia with naloxone. Anesthesiology 41: 361–367 (1974).

    PubMed  CAS  Google Scholar 

  • Jordan, C.: Respiratory depression following diazepam: Reversal with high-dose naloxone. Anesthesiology 53: 293–298 (1980).

    PubMed  CAS  Google Scholar 

  • Kamerling, S.G.; Martin, W.R.; Wu, K.M. and Wettstein, J.G.: Medullary κ hyperalgesic mechanisms. II. The effects of ethylketazocine administered into the fourth cerebral ventricle of the conscious dog. Life Sciences 33: 1839–1843 (1983).

    PubMed  CAS  Google Scholar 

  • Kleinman, J.E.; Weinberger, D.R.; Rogol, A.; Shiling, D.J.; Mendelson, W.B.; Davis, G.C.; Bunney, W.E. Jr and Wyatt, R.J.: Naloxone in chronic schizophrenic patients: Neuroendocrine and behavioral effects. Psychiatry research 7: 1–7 (1982).

    PubMed  CAS  Google Scholar 

  • Kryger, M.H.; Yacoub, O.; Dosman, J.; Macklem, P.T. and Anthonisen, N.R.: Effect of meperidine on occlusion pressure responses to hypercapnia and hypoxia with and without external inspiratory resistance. American Review of Respiratory Diseases 114: 333–340 (1976).

    CAS  Google Scholar 

  • Landmesser, C.M.; Formel, P.F. and Converse, J.G.: Comparative effects of a new narcotic antagonist (levallorphan tartrate) upon the respiratory responses to carbon dioxide during narcotic and barbiturate depression in anesthetized man. Anesthesiology 16: 520–535 (1955).

    PubMed  CAS  Google Scholar 

  • Lasagna, L.: Drug interaction in the field of analgesic drugs. Proceedings of the Royal Society of Medicine 58: 978–983 (1965).

    PubMed  CAS  Google Scholar 

  • Lasagna, L. and Beecher, H.K.: The analgesic effectiveness of nalorphine and nalorphine-morphine combinations in man. Journal of Pharmacology and Experimental Therapeutics 112: 356–363 (1954).

    PubMed  CAS  Google Scholar 

  • Laubie, M.; Schmitt, H.; Canellas, J.; Roquebert, J. and Demichel, P.: Centrally mediated bradycardia and hypotension induced by narcotic analgesics: dextromoramide and fentanyl. European Journal of Pharmacology 28: 66–75 (1974).

    PubMed  CAS  Google Scholar 

  • Laubie, M.; Schmitt, H. and Vincent, M.: Vagal bradycardia produced by microinjections of morphine-like drugs into the nucleus ambiguus in anaesthetized dogs. European Journal of Pharmacology 59: 287–291 (1979).

    PubMed  CAS  Google Scholar 

  • Laubie, M.; Schmitt, H.; Vincent, M. and Remond, G.: Central cardiovascular effects of morphinomimetic peptides in dogs. European Journal of Pharmacology 46: 67–71 (1977).

    PubMed  CAS  Google Scholar 

  • Lawson, E.E.; Waldrop, T.G. and Eldridge, F.L.: Naloxone enhances respiratory output in cats. Journal of Applied Physiology: Respiratory Environmental and Exercise Physiology 47: 1105–1111 (1979).

    CAS  Google Scholar 

  • Lehmann, H.; Nair, V. and Kline, N.S.: β-Endorphin and naloxone in psychiatric patients: Clinical and biological effects. American Journal of Psychiatry 136: 762–766 (1979).

    PubMed  CAS  Google Scholar 

  • Lenz, K.; Druml, W.; Gassner, A.; Hruby, K.; Kleinberger, G. and Laggner, A.: Naloxone in shock (correspondence). Lancet 1: 834 (1981).

    PubMed  CAS  Google Scholar 

  • Lindeburg, T.; Larsen, V.; Kehlet, H. and Jacobsen, E.: Respiratory, analgesic and endocrine responses to an enkephalin analogue in normal man. Acta Anaesthesiologica Scandinavica 25: 254–257 (1981).

    PubMed  CAS  Google Scholar 

  • Lindström, L.H.; Widerlöv, E.; Gunne, I-M.; Wahlström, A. and Terenius, L.: Endorphins in human cerebrospinal fluid: Clinical correlations to some psychotic states. Acta Psychiatrica Scandinavica 57: 153–164 (1978).

    PubMed  Google Scholar 

  • Lipinski, J.; Meyer, R.; Kornetsky, C. and Cohen, B.M.: Naloxone in schizophrenia: Negative result. Lancet 1: 1292–1293 (1979).

    PubMed  CAS  Google Scholar 

  • Longnecker, D.E.; Grazis, P.A. and Eggers, G.W.N.: Naloxone for antagonism of morphine-induced respiratory depression. Anesthesia and Analgesia 52: 447–453 (1973).

    PubMed  CAS  Google Scholar 

  • Lord, J.A.H.; Waterfield, A.A.; Hughes, J. and Kosterlitz, H.W.: Endogenous opioid peptides: Multiple agonists and receptors. Nature 267: 495–499 (1977).

    PubMed  CAS  Google Scholar 

  • Martin, W.R.: Opioid antagonists. Pharmacological Reviews 19: 463–521 (1967).

    PubMed  CAS  Google Scholar 

  • Martin, W.R.: A homeostatic and redundancy theory of tolerance to and dependence on narcotic analgesics; in Wikler (Ed.), the Addictive States — Association for Research in Nerve and Mental Disease, Volume XLVI, pp.206–225 (Williams and Wilkins Company, Baltimore 1968).

    Google Scholar 

  • Martin, W.R.; Eades, C.G.; Gilbert, P.E. and Thompson, J.A.: Tolerance to and physical dependence on N-allylnormetazocine (NANM) in chronic spinal dogs. Substance and Alcohol Actions/Misuse 1: 269–279 (1980).

    PubMed  CAS  Google Scholar 

  • Martin, W.R.; Eades, C.G.; Thompson, J.A.; Huppier, R.E. and Gilbert, P.E.: The effects of morphine- and nalorphine-like drugs in the nondependent and morphine-dependent chronic spinal dog. Journal of Pharmacology and Experimental Therapeutics 197: 517–532 (1976).

    PubMed  CAS  Google Scholar 

  • Martin, W.R. and Eisenman, A.J.: Interactions between nalorphine and morphine in the decerebrate cat. Journal of Pharmacology and Experimental Therapeutics 138: 113–119 (1962).

    CAS  Google Scholar 

  • Martin, W.R.; Jasinski, D.R. and Mansky, P.A.: Naltrexone, an antagonist for the treatment of heroin dependence. Archives of General Psychiatry 28: 784–791 (1973).

    PubMed  CAS  Google Scholar 

  • Mattila, M.J.; Nuotto, E. and Seppälä, T.: Naloxone is not an effective antagonist of ethanol. Lancet 1: 775–776 (1981).

    PubMed  CAS  Google Scholar 

  • McAllen, R. and Spyer, K.: The location of cardiac vagal preganglionic motoneurones in the medulla of the cat. Journal of Physiology (London) 258: 187–204 (1976).

    CAS  Google Scholar 

  • Miclke, D.H. and Gallant, D.M.: An oral opiate antagonist in chronic schizophrenia: A pilot study. American Journal of Psychiatry 134: 1430–1431 (1977).

    Google Scholar 

  • Moss, I.R. and Friedman, E.: β-Endorphin: Effects on respiratory regulation. Life Sciences 23: 1271–1276 (1978).

    PubMed  CAS  Google Scholar 

  • Moss, L.M.: Naloxone reversal of non-narcotic induced apnea. Journal of the American College of Emergency Physicians 1: 46 (1973).

    Google Scholar 

  • Pazos, A. and Flórez, J.: Interaction of naloxone with μ- and δopioid agonists on the respiration of rats. European Journal of Pharmacology 87: 309–314 (1983).

    PubMed  CAS  Google Scholar 

  • Peters, W.P.; Friedman, P.A.; Johnson, M.W. and Mitch, W.E.: Pressor effect of naloxone in septic shock. Lancet 1: 529–532 (1981).

    PubMed  CAS  Google Scholar 

  • Pickar, D.; Vartanian, F.; Bunney, W.E. Jr; Maier, H.P.; Gastpar, M.T.; Prakash, R.; Sethi, B.B.; Lideman, R.; Belyaev, B.S.; Tsutsulkovskaja, M.V.A.; Jungkunz, G.; Nedopil, N.; Verhoeven, W. and van Praag, H.: Short-term naloxone administration in schizophrenic and manic patients. A World Health Organization Collaborative Study. Archives of General Psychiatry 39: 313–319 (1982).

    PubMed  CAS  Google Scholar 

  • Pohl, J.: Uber das N-allylnorcodeine, einen antagonisten des Morphins. Zeitschrift Gesamte Experimentelle Medizin 17: 370–378 (1915).

    Google Scholar 

  • Reynolds, D.G.; Gurll, N.J.; Vargish, T.; Lechner, R.B.; Faden, A.I. and Holaday, J.W.: Blockade of opiate receptors with naloxone improves survival and cardiac performance in canine endotoxic shock. Circulatory Shock 7: 39–48 (1980).

    PubMed  CAS  Google Scholar 

  • Santiago, T.V.: Endorphins and the control of breathing. Ability of naloxone to restore flow-resistive load compensation in chronic obstructive pulmonary disease. New England Journal of Medicine 304: 1190–1195 (1981).

    PubMed  CAS  Google Scholar 

  • Simpson, G.M.; Branchey, M.H. and Lee, J.H.: A trial of naltrexone in chronic schizophrenia. Current Therapeutic Research 22: 909–913 (1977).

    Google Scholar 

  • Smith, R.A.; Wilson, M. and Miller, K.W.: Naloxone has no effect on nitrous oxide anesthesia. Anesthesiology 49: 6–8 (1978).

    PubMed  CAS  Google Scholar 

  • Sørensen, S.C. and Mattisson, K.W.: Naloxone as an antagonist in severe alcohol intoxication. Lancet 2: 688–689 (1978).

    PubMed  Google Scholar 

  • Sowell, J.H.; Bowen, S.R. and Carpenter, F.G.: Hyperventilation in rats treated with morphine and naloxone. Federation Proceedings 38: 681 (1979).

    Google Scholar 

  • Terenius, L.; Wahlström, A.; Lindström, L. and Widerlöv, E.: Increased CSF levels of endorphins in chronic psychosis. Neuroscience Letters 3: 157–162 (1976).

    PubMed  CAS  Google Scholar 

  • Teschemacher, H.; Schubert, P. and Herz, A.: Autoradiographic studies concerning the supraspinal site of the antinociceptive action of morphine when inhibiting the hindleg flexor reflex in rabbits. Neuropharmacology 12: 123–131 (1973).

    PubMed  CAS  Google Scholar 

  • Tiengo, M.: Naloxone in irreversible shock (correspondence). Lancet 2: 690 (1980).

    PubMed  CAS  Google Scholar 

  • Unna, K.: Antagonistic effect of N-allyl-normorphine upon morphine. Journal of Pharmacology and Experimental Therapeutics 79: 27–31 (1943).

    CAS  Google Scholar 

  • Vargish, T.; Reynolds, D.G.; Gurll, N.J.; Lechner, R.B.; Holaday, J.W. and Faden, A.I.: Naloxone reversal of hypovolemic shock in dogs. Circulatory Shock 7: 31–38 (1980).

    PubMed  CAS  Google Scholar 

  • Vaupel, D.B.: Failure of naltrexone (NTX) to antagonize phencyclidine (PCP) and the opioid SKF 10047 (SKF) in the dog. Federation Proceedings 41: 1333 (1982).

    Google Scholar 

  • Vaupel, D.B. and Jasinski, D.R.: Acute single dose effects of phencyclidine (PCP) in the dog. Federation Proceedings 38: 435 (1979).

    Google Scholar 

  • Volavka, J.; Mallya, A.; Baig, S. and Perez-Cruet, J.: Naloxone in chronic schizophrenia. Science 196: 1227–1228 (1977).

    PubMed  CAS  Google Scholar 

  • Wahlslröm, A.; Johansson, L. and Terenius, L.: Characterization of endorphins (endogenous morphine-like factors) in human CSF and brain extracts; in Koslerlitz (Ed) Opiates and Endogenous Opioid peptides (Elsevier/North Holland Biomedical Press, Amsterdam 1976).

    Google Scholar 

  • Walz, M.A. and Davis, W.M.: Experimental diazepam intoxication in rodents: Physostigmine and naloxone as potential antagonists. Drug and Chemical Toxicology 2: 257–267 (1979).

    PubMed  CAS  Google Scholar 

  • Watson, S.J.; Berger, P.A.; Akil, H.; Mitts, M.J. and Barchas, J.D.: Effects of naloxone on schizophrenia: Reduction in hallucinations in a subpopulation of subjects. Science 201: 73–76 (1978).

    PubMed  CAS  Google Scholar 

  • Weijlard, J. and Erickson, A.E.: N-Allylnormorphine. Journal of the American Chemical Society 64: 869–870 (1942).

    CAS  Google Scholar 

  • Weil, J.V.; McCullough, R.E.; Kline, J.S. and Sodal, I.E.: Diminished ventilatory response to hypoxia and hypercapnia after morphine in normal man. New England Journal of Medicine 292: 1103–1106 (1975).

    PubMed  CAS  Google Scholar 

  • Wright, D.J.M.; Phillips, M. and Weller, M.P.I.: Naloxone in shock (correspondence). Lancet 2: 1361 (1980).

    Google Scholar 

  • Wu, K.M. and Martin, W.R.: Effects of naloxone and fentanyl in the acutely decerebrated dog. Life Sciences (In press 1983a).

    Google Scholar 

  • Wu, K.M. and Martin, W.R.: An analysis of nicotinic and opioid processes in the medulla oblongata and nucleus ambiguus of the dog. Journal of Pharmacology and Experimental Therapeutics 227: 302–307 (1983b).

    PubMed  CAS  Google Scholar 

  • Wu, K.M.; Martin, W.R.; Kamerling, S.G. and Wettstein, J.G.: Possible medullary κ hyperalgesic mechanism. I. A new potential role for endogenous opioid peptides in pain perception. Life Sciences 33: 1831–1838 (1983).

    PubMed  CAS  Google Scholar 

  • Yaksh, T.L.: Spinal opiate analgesia: Characteristics and principles of action. Pain 11: 293–346 (1981).

    PubMed  CAS  Google Scholar 

  • Young, W.; Flamm, E.S.; Demopoulos, H.G.; Tomasula, J.H. and DeCrescito, V.: Effect of naloxone on posttraumatic ischemia in experimental spinal contusion. Journal of Neurosurgery 55: 209–219 (1981).

    PubMed  CAS  Google Scholar 

  • Zobrist, R.H.; Allerton, H.W. and Isom, G.E.: Characterization of the respiratory activity of (D-Ala1)methionine-enkephali-namide. European Journal of Pharmacology 70: 121–128 (1981).

    PubMed  CAS  Google Scholar 

  • Zukin, S.R. and Zukin, R.S.: Specific [3H]-phencyclidine binding in rat central nervous system. Proceedings of the National Academy of Sciences USA 76: 5372–5376 (1979).

    CAS  Google Scholar 

  • Zukin, S.R. and Zukin, R.S.: [3H]-phencyclidine binding to specific brain receptor sites. Psychopharmacology Bulletin 16: 59–62 (1980).

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Kentucky College of Medicine, Research Facility No. 2, MR-109, Lexington, Kentucky, 40536, USA

    L. F. McNicholas & W. R. Martin

Authors
  1. L. F. McNicholas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. R. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

McNicholas, L.F., Martin, W.R. New and Experimental Therapeutic Roles for Naloxone and Related Opioid Antagonists. Drugs 27, 81–93 (1984). https://doi.org/10.2165/00003495-198427010-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-198427010-00004

Keywords

Search

Navigation