Lithium pp 51-73 | Cite as

Pharmacology—The Effects of Lithium on Biogenic Amines

  • Joseph J. Schildkraut


Since the initial report (Schildkraut, 1966) that acute administration of lithium salts altered the metabolism of norepinephrine in rat brain, numerous other studies have examined the effects of lithium salts on the turnover and metabolism of biogenic amines both in animal brain and in human subjects. This chapter will concern itself with the findings of these studies, which have also been considered in other recent reviews (e.g., Schildkraut, 1970; Fieve, 1970–1971; Gershon, 1970; Davis and Fann, 1971).


Biogenic Amine Lithium Chloride Lithium Level Lithium Salt Animal Brain 
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  1. Baldessarini, R. J., and Yorke, C., 1970, Effects of lithium and of pH on synaptosomal metabolism of noradrenaline, Nature 228:1301.PubMedCrossRefGoogle Scholar
  2. Bindler, E. H., Wallach, M. B., and Gershon, S., 1971, Effect of lithium on the release of 1C-norepinephrine by nerve stimulation from the perfused cat spleen, Arch. Int. Pharmacol. Therap. 190:150.Google Scholar
  3. Bliss, E. L., and Ailion, J., 1970, The effect of lithium upon brain neuroamines. Brain Res. 24:305.PubMedCrossRefGoogle Scholar
  4. Bowers, M. B., Jr., Heninger, G. R., and Gerbode, F., 1969, Cerebrospinal fluid 5-hydroxy- indoleacetic acid and homovanillic acid in psychiatric patients. Int. J. Neuropharmacol. 8:255.PubMedCrossRefGoogle Scholar
  5. Carroll, B. J., and Sharp, P. T., 1972, Rubidium and lithium: opposite effects on amine- mediated excitement, Science 172:1355.CrossRefGoogle Scholar
  6. Colburn, R. W., Goodwin, F. K., Bunney, W. E., Jr., and Davis, J. M., 1967, Effect of lithium on uptake of noradrenaline by synaptosomes. Nature 215:1395.PubMedCrossRefGoogle Scholar
  7. Corrodi, H., Fuxe, K., Hokfelt, T., and Schou, M., 1967, Effect of lithium on cerebral monoamine neurons, Psychopharmacologia 11:345.PubMedCrossRefGoogle Scholar
  8. Corrodi, H., Fuxe, K., and Schou, M., 1969, The effect of prolonged lithium administration on cerebral monoamine neurons in the rat. Life Sci. 8:643.PubMedCrossRefGoogle Scholar
  9. Costa, E., 1972, Appraisal of current methods to estimate the turnover rate of serotonin and catecholamines in human brain, in: Advances in Biochemical Psychopharmacology, Vol. 4, pp. 171–183, Raven Press, New York.Google Scholar
  10. Costa, E., and Neff, N. H., 1970, Estimation of turnover rates to study the metabolic regulation of the steady-state level of neuronal monoamines, in:Handbook of Neuro-chemistry. Vol. 4 (A. Lajtha, ed.) pp. 45–90, Plenum Press, New York.Google Scholar
  11. Davis, J. M., and Fann, W. E., 1971, Lithium, Ann. Rev. Pharmacol. 11:285.PubMedCrossRefGoogle Scholar
  12. D’Encarnacao, P. S., and Anderson, K., 1970, Effects of lithium pretreatment on amphetamine and DM I tetrabenazine-produced psychomotor behavior. Diseases Nervous System 31:494.Google Scholar
  13. Detre, T., Himmelhoch, J., Swartzburg, M., Anderson, C. M., Byck, R., and Kupfer, D., 1972, Hypersomnia and manic-depressive disease, Am. J. Psychiat. 128:1303.PubMedGoogle Scholar
  14. Dousa, T., and Hechter, O., 1970, Lithium and brain adenyl cyclase. Lancet 1:834.PubMedGoogle Scholar
  15. Fann, W. E., Davis, J. M., Janowsky, D. S., Cavanaugh, J. H., Kaufmann, J. S., Griffith, J. D., and Oates, J. A., 1972, Effects of lithium on adrenergic function in man, Clin. Pharmacol. Therap. 13:71.Google Scholar
  16. Fieve, R. R., 1970–1971, Lithium in psychiatry. Int. J. Psychiat. 9:375.Google Scholar
  17. Forn, J., and Valdecasas, F. G., 1971, Effects of lithium on brain adenyl cyclase activity, Biochem. Pharmacol. 20:2773.PubMedCrossRefGoogle Scholar
  18. Gershon, S., 1970, Lithium in mania. Clin. Pharmacol. Therap. 11:168.Google Scholar
  19. Greenspan, K., Aronoff, M. S., and Bogdanski, D. F., 1970a, Effects of lithium carbonate on turnover and metabolism of norepinephrine in rat brain—correlation to gross behavioral effects. Pharmacology 3:129.CrossRefGoogle Scholar
  20. Greenspan, K., Schildkraut, J. J., Gordon, E. K., Baer, L., Aronoff, M. S., and Durell, J., 1970b, Catecholamine metabolism in affective disorders. III. MHPG and other catecholamine metabolites in patients treated with lithium carbonate, J. Psychiat. Res. 7:171.PubMedCrossRefGoogle Scholar
  21. Harrison-Read, P. E., and Steinberg, H., 1971, Lithium-induced hypersensitivity to foot shock in rats and the role of 5-hydroxytryptophan, Nature (New Biol.) 232:120.CrossRefGoogle Scholar
  22. Haskovec, L., and Rysanek, K., 1969, Die Wirkung von Lithium auf den Metabolismus der Katecholamine und Indolalkylamine beim Menschen, Arzneimittel-Forsch. 19:426.Google Scholar
  23. Himmelhoch, J. M., Detre, T., Kupfer, D. J., and Byck, R., 1972, Treatment of previously intractable depressions with tranylcypromine and lithium, J. Nerv. Ment. Dis. 155:216.PubMedCrossRefGoogle Scholar
  24. Ho, A. K. S., Loh, H. H., Craves, F., Hitzemann, R. J., and Gershon, S., 1970, The effect of prolonged lithium treatment on the synthesis rate and turnover of monoamines in brain regions of rats, European J. Pharmacol. 10:72.CrossRefGoogle Scholar
  25. Iversen, L. L., and Bloom, F. E., 1970, Transmitter release mechanisms, Neurosci. Res. Prog. Bull. 8:407.Google Scholar
  26. Katz, R. I., and Kopin, I. J., 1969, Release of norepinephrine-3H and serotonin-3H evoked from brain slices by electrical-field stimulation—calcium dependency and the effects of lithium, ouabain, and tetrodotoxin, Biochem. Pharmacol. 18:1935.CrossRefGoogle Scholar
  27. Katz, R. I., Chase, T. N., and Kopin, I. J., 1968, Evoked release of norepinephrine and serotonin from brain slices: inhibition by lithium, Science 162:466.PubMedCrossRefGoogle Scholar
  28. Kiseleva, I. P., and Lapin, I. P., 1969, Antagonistic effect of lithium carbonate on 5- hydroxytryptophan-induced head-twitches in mice, Pharmacol. Res. Commun. 1:108.CrossRefGoogle Scholar
  29. Kuriyama, K., and Speken, R., 1970, Effect of lithium on content and uptake of norepinephrine and 5-hydroxytryptamine in mouse brain synaptosomes and mitochondria. Life Sci. 9:1213.CrossRefGoogle Scholar
  30. Maas, J. W., and Landis, D. H., 1968, In vivo studies of metabolism of norepinephrine in central nervous system, J. Pharmacol. Exptl. Therap. 163:147.Google Scholar
  31. Mannarino, E., Kirshner, N., and Nashold, B. S., Jr., 1963, Metabolism of (C-14) noradrenaline by cat brain in vivo, J. Neurochem. 10:373.CrossRefGoogle Scholar
  32. Matussek, N., and Linsmayer, M., 1968, The effect of lithium and amphetamine on desmethylimipramine-RO 4–1284 induced motor hyperactivity. Life Sci. 7:371.PubMedCrossRefGoogle Scholar
  33. Mendels, J., 1971, Relationship between depression and mania, Lancet 1:342.PubMedCrossRefGoogle Scholar
  34. Messiha, F. S., Agallianos, D., and Clower, C., 1970, Dopamine excretion in affective states and following Li2Co3 therapy. Nature 225:868.PubMedCrossRefGoogle Scholar
  35. Murphy, D. L., and Weiss, R., 1972, Reduced monoamine oxidase activity in blood platelets from bipolar depressed patients. Am. J. Psychiat. 128:1351.PubMedGoogle Scholar
  36. Murphy, D. L., Colburn, R. W., Davis, J. M., and Bunney, W. E., Jr., 1969, Stimulation by lithium of monoamine uptake in human platelets. Life Sci. 8:1187.PubMedCrossRefGoogle Scholar
  37. Perez-Cruet, J., Tagliamonte, A., Tagliamonte, P. and Gessa, G. L., 1971, Stimulation of serotonin synthesis by lithium, J. Pharmacol. Exptl. Therap. 178:325.Google Scholar
  38. Persson, T., 1970, Drug induced changes in 3H-catecholamine accumulation after 3H- tyrosine. Acta Pharmacol. Toxicol, 28:378.CrossRefGoogle Scholar
  39. Pick, G., and Mills, W. A., 1971, The effects of lithium and amphetamine on threshold of intracranial reinforcement, Presented at the 42nd Annual Meeting of the Eastern Psychological Association.Google Scholar
  40. Sanghvi, I., Urquiaga, X., and Gershon, S., 1970, The effect of acute and chronic lithium administration on the superior cervical ganglion of the cat, Pharmacol. Res. Commun. 2:361.CrossRefGoogle Scholar
  41. Schanberg, S. M., Breese, G. R., Schildkraut, J. J., Gordon, E. K., and Kopin, I. J., 1968a, 3-Methoxy-4-hydroxyphenylglycol sulfate in brain and cerebrospinal fluid, Biochem. Pharmacol. 17:2006.Google Scholar
  42. Schanberg, S. M., Schildkraut, J. J., Breese, G. R., and Kopin, I. J., 1968b, Metabolism of normetanephrine-H3 in rat brain: identification of conjugated 3-methoxy-4-hydroxy- phenylglycol as major metabolite, Biochem. Pharmacol. 17:247.PubMedCrossRefGoogle Scholar
  43. Schildkraut, J. J., 1970, Neuropsychopharmacology and the Affective Disorders, Little, Brown and Company, Boston.Google Scholar
  44. Schildkraut, J. J., in press. The effects of lithium on norepinephrine turnover and metabolism: basic and clinical studies, J. Nerv. Mem. Dis.Google Scholar
  45. Schildkraut, J. J., Schanberg, S. M., and Kopin, T. J., 1966, The effects of lithium ion on H-norepinephrine metabolism in brain. Life Sci. 5:1479.PubMedCrossRefGoogle Scholar
  46. Schildkraut, J. J., Schanberg, S. M., Breese, G. R., and Kopin, I. J., 1967, Norepinephrine metabolism and drugs used in the affective disorders: a possible mechanism of action. Am. J. Psychiat. 124:600.PubMedGoogle Scholar
  47. Schildkraut, J. J., Dodge, G. A., and Logue, M. A., 1969a, Effects of tricyclic antidepressants on uptake and metabolism of intracisternally administered norepinephrine-H3 in rat brain, J. Psychiat. Res. 7:29.PubMedCrossRefGoogle Scholar
  48. Schildkraut, J. J., Logue, M. A., and Dodge, G. A., 1969b, Effects of lithium salts on turnover and metabolism of norepinephrine in rat brain, Psychopharmacologia 14:135.PubMedCrossRefGoogle Scholar
  49. Schildkraut, J. J., Schanberg, S. M., Breese, G. R., and Kopin, L J., 1969c, Effects of psychoactive drugs on the metabolism of intracisternally administered serotonin in rat brain, Biochem. Pharmacol. 18:1971.PubMedCrossRefGoogle Scholar
  50. Schildkraut, J. J., Winokur, A., Draskoczy, P. R., and Hensle, J. H., 1971, Changes in norepinephrine turnover in rat brain during chronic administration of imipramine and protriptyline: a possible explanation for the delay in onset of clinical antidepressant effects. Am. J. Psychiat. 27:1032.Google Scholar
  51. Sheard, M., 1970, Behavioral effects of p-chlorophenylalanine in rats: inhibition by lithium, Commun. Behav. Biol. 5:71.Google Scholar
  52. Sheard, M. H. and Aghajanian, G. K., 1970, Neuronally activated metabolism of brain serotonin: effect of lithium. Life Sci. 9:285.PubMedCrossRefGoogle Scholar
  53. Stein, L., 1969, Psychopharmacological substrates of mental depression, in: Antidepressant Drugs (S. Garattini and M. N. G. Dukes, eds.), pp. 130–140, Excerpta Medica, Amsterdam.Google Scholar
  54. Stern, D. N., Fieve, R. R., Neff, N. H., and Costa, E., 1969, The effect of lithium chloride administration on brain and heart norepinephrine turnover rates, Psychopharmacologia 14:315.PubMedCrossRefGoogle Scholar
  55. Wilk, S., Shopsin, B., Gershon, S., and Suhl, M., 1972, Cerebrospinal fluid levels of MHPG in affective disorders. Nature 235:440.PubMedCrossRefGoogle Scholar
  56. Zall, H., 1971, Lithium carbonate and isocarboxazid—an effective drug approach in severe depressions. Am. J. Psychiat. 127:10.Google Scholar

Copyright information

© Plenum Press, New York 1973

Authors and Affiliations

  • Joseph J. Schildkraut
    • 1
  1. 1.Neuropsychopharmacology Laboratory, Massachusetts Mental Health Center, Department of PsychiatryHarvard Medical SchoolBostonUSA

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