Neuroleptics — Allosteric Tyrosine Hydroxylase Regulators

  • M. F. Mineyeva
  • V. S. Kudrin
  • A. Yu. Shemanov


The action of psychotropic compounds on catecholaminergic processes is a key factor in their action on the function of the central and peripheral nervous system (Zakusov, 1973; Valdman et al., 1979; Breese et al., 1978; Bunney and Aghajanian, 1975), since impairment of these processes may be an important stage in the onset and development of schizophrenia and other psychoses (Owen et al., 1978; Snyder, 1974; Lideman et al., 1980; Le Fur et al., 1979).


Tyrosine Hydroxylase Substrate Inhibition Dopamine Receptor Agonist Dopamine Receptor Antagonist Presynaptic Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Ahlenius, S., 1974, Reversal by DOPA of the suppression of locomotor activity induced by inhibition of tyrosine hydroxylase and dopamine 3-hydroxylase in mice, Brain Res, 79:57–65.CrossRefGoogle Scholar
  2. Annunziato, L., Cerrito, F., and Raiteri, M., 1981, Characteristics of dopamine release from isolated nerve endings of the tubero-infundibular neurones, Neuropharmacology., 20:727–731.PubMedCrossRefGoogle Scholar
  3. Antelman, S. M., Szechtman, H., Chin, P., and Fisher, A. E., 1976, Inhibition of tyrosine hydroxylase but not dopaminehydroxylase facilitates the action of behaviourally ineffective doses of neuroleptics, J.Pharm.Pharmacol., 28:66–68.PubMedCrossRefGoogle Scholar
  4. Bradford, H. V., 1970, Metabolic response of synaptosomes to electrical stimulation release of amino acids, Brain Res., 19:239–247.PubMedCrossRefGoogle Scholar
  5. Breese, G. R., Mueller, R. A., Hollister, A., and Mailman, R., 1978, Importance of dopaminergic pathways and other neural systems to behaviour and action of psychotropic drugs, Fed.Proc., 37:10:2429–2433.PubMedGoogle Scholar
  6. Coyle, J. T., 1972, Tyrosine hydroxylase in rat brain — cofactor requirements, regional and subcellular distribution, Biochem. Pharmacol., 21:1935–1944.PubMedCrossRefGoogle Scholar
  7. Di Chiara, G., Corsini, G. U., Mereu, G. P., Tissari, A., and Gessa, G. L., 1978, Self-inhibitory dopamine receptors: their role in the biochemical and behavioural effects of low doses of apomorphine, in: “Dopamine 2. Advances in Biochemical Psycho-pharmacology,” P. J. Roberts, G. N. Woodruff, and L. L. Iversen, eds., vol. 19, Raven Press, New York, pp. 273–295.Google Scholar
  8. Demarest, K. T., and Moore, K. E., 1979, Comparison of dopamine synthesis regulation in the terminals of nigrostriatal, mesolimbic, tuberoinfundibular and tuberohypophyseal neurons, J.Neural Transmiss., 46:263–277.CrossRefGoogle Scholar
  9. George, S. R., and Van Loon, G. R., 1982, Characterization of high affinity dopamine uptake into the dopamine neurones of the hypothalamus, Brain Res., 234:339–355.PubMedCrossRefGoogle Scholar
  10. Glowinski, J., and Iversen, L. L., 1966, Regional studies of catecholamines in the rat brain, I. The disposition of 3H-norepinephrine, 3H-dopamine and 3H-DOPA in various regions of the brain, J.Neurochem., 13:655–669.PubMedCrossRefGoogle Scholar
  11. Gray, E. G., and Whittaker, V. P., 1962, The isolation of nerve endings from brain: an electron-microscopic study of cell fragments derived by homogenization and centrifugation, J.Anat., 96:79–87.PubMedGoogle Scholar
  12. Hajos, T., 1975, An improved method for the preparation of synaptosomal fractions in high purity, Brain Res., 93:485–489.PubMedCrossRefGoogle Scholar
  13. Horn, A. S., Cuello, A. S., and Miller, R. J., 1974, Dopamine in the mesolimbic system of the rat brain: endogenous levels and the effects of drugs on the uptake mechanism and stimulation of adenylate cyclase activity, J.Neurochem, 22:265–270.PubMedCrossRefGoogle Scholar
  14. Karobath, W. E., 1975, Dopamine-Receptor Blockade, ein moglicher Wirkungsmechanismus antipsychotisch wirksamer Pharmaka, Pharmacopsychiatrie, 8:152–161.Google Scholar
  15. Kuchenski, R., and Mandell, A. J., 1972, Regulatory properties of soluble and particulate rat brain tyrosine hydroxylase, J.Biol.Chem., 247:3114–3122.Google Scholar
  16. Kuchenski, R., and Segal, D. S., 1974, Intrasynaptosomal conversion of tyrosine to dopamine as an index of brain catecholamine biosynthetic capacity, J.Neurochem. 22:1039–1044.CrossRefGoogle Scholar
  17. Lachti, N. A., and Gay, D. D., 1982, Lack of effect of des-tyrendorphin on in vivo 3H-spiperone binding, Eur.J.Pharmacol., 80:127–131.CrossRefGoogle Scholar
  18. Lasar, M. A., Mefford, J. N., Barchas, J. D., 1982, Comparison of in vitro phosphorylation and in vivo administration of haloperidol, Biochem.Pharmacol., 31:2599–2609.CrossRefGoogle Scholar
  19. Le Fur, G., Guillouz, F., and Uzan, A., 1980, In vivo blockade of dopaminergic receptors from different rat brain regions by classical and atypical neuroleptics, Biochem.Pharmacol., 29:267–270.PubMedCrossRefGoogle Scholar
  20. Levitt, M., Spector, S., Sjoerdsma, A., and Udenfriend, S., 1965, Elucidation of the rate limiting step in noradrenaline biosynthesis in the perfused guinea pig heart, J.Pharmacol.Exp.Ther., 148:1–8.PubMedGoogle Scholar
  21. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J., 1951, Protein measurement with Folin phenol reagent, J.Biol.Chem., 193:263–275.Google Scholar
  22. Mager, H. I., Addink, R., and Berends, W., 1967, Coupled and decoupled processes in the autooxidation of partially reduced pteridines and flavins, Rec.Trav.chim.Pays-Bas, 86:833–851.CrossRefGoogle Scholar
  23. Mandell, A., 1978, Redundant mechanisms regulating brain tyrosine and tryptophan hydroxylases, Ann.Rev.Pharmacol.Toxicol., 18:461–493.CrossRefGoogle Scholar
  24. McGregor, W. H., Stein, I., and Beluzzi, J. D., 1978, Potent analgesic activity of the enkephaline-like tetrapeptide H-tyr-D-Ala-Gly-PheNH2 Life Sci., 23:1371–1378.PubMedCrossRefGoogle Scholar
  25. Mineyeva, M. F., Tummler, D., Kuznetsova, E. A., Vassiliev, A. E., and Rayevski, K. S., 1982, Change in kinetic properties of tyrosine hydroxylase due to dopamine effect on the external synaptosomal membrane, Ann.1st.Super.Sanita 18:45–48.Google Scholar
  26. Murrin, L. C., Morgenroth III V. H., and Roth, R. H., 1976, Dopaminergic neurons: effects of electrical stimulation on tyrosine hydroxylase, Molec.Pharmacol., 12:1070–1081.Google Scholar
  27. Nagatsu, T., Levitt, M., and Udenfriend, S., 1964, A rapid and simple radioassay for tyrosine hydroxylase activity, Analyt.Biochem., 9:122–126.PubMedCrossRefGoogle Scholar
  28. Owen, F., Crow, T. J., Poulter, M., Cross, A. J., Longden, A., and Riley, G. J., 1978, Increased dopamine receptor sensitivity in schizophrenia, Lancet ii:223–226.CrossRefGoogle Scholar
  29. Pegigo, N. W., Schallert, T., Overstreet, D. H., Ling, N. C, Ragan, P., Reisine T., and Yamamura, H. I., 1979, Inhibition of in vitro 3H-spiperone binding by the proposed antipsychotic des-tyrendorphin, Eur.J.Pharmacol., 60:359–364.CrossRefGoogle Scholar
  30. Poshel, B. P., and Nitelman, F. W., 1966, Hypothalamic self-stimulation: its suppression by blockade of norepinephrine biosynthesis and reinstatement by methamphetamine, Life Sci., 5:11–16.CrossRefGoogle Scholar
  31. Reisine, T. D., Pedigo, N. W., Ragan, P., Ling, N., and Yamamura, H. I., 1979, Abnormal brain opiate mechanisms in schizophrenia, in: “Endogenous and Exogenous Opiate Agonists and Antagonists,” Proc.Int.Narcotic Res., North Falmouth, Mass, 1980, pp.117–120.Google Scholar
  32. Snyder, S., 1976, The dopamine hypothesis of schizophrenia: focus on the dopamine receptor, Am.J.Psychiatry, 133:197–202.PubMedGoogle Scholar
  33. Tuomisto, J., 1978, Neurophysiological intervention on the pituitary-hypothalamic relationship, Ann.Clin.Res., 10:120–132.PubMedGoogle Scholar
  34. Venter, J., Diton, J. S., Maroko, P. R., and Kaplan, N. O., 1975, Biologically active catecholamines covalently bound to glass beads, Proc.Nat.Acad.Sci.USA., 69:1141–1145.CrossRefGoogle Scholar
  35. Wied, De D., Kovacs, G. L., Bohus, B., van Ree, J. M., and Greven, H. M., 1978, Neuroleptic activity of the neuropeptide γ-LPH 62–67 (des-Tyr-γ-endorphin: DT E), Eur.J.Pharmacol., 49:427–426.PubMedCrossRefGoogle Scholar
  36. Wied, De D., 1979, Schizophrenia as an inborn error in the degradation of γ-endorphin — a hypothesis. Trends Neurosci. 49:79–82.CrossRefGoogle Scholar
  37. Zivkovic, B., Guidotti, A., Revetta, A., and Costa, E., 1975, Effect of thioridazine, clozapine and other antipsychotics on the kinetic state of tyrosine hydroxylase and on the turnover rate of dopamine in striatum and nucleus accumbens, J.Pharmacol.Exp.Ther., 194:37–46.PubMedGoogle Scholar

Copyright information

© Consultants Bureau, New York 1986

Authors and Affiliations

  • M. F. Mineyeva
    • 1
  • V. S. Kudrin
    • 1
  • A. Yu. Shemanov
    • 1
  1. 1.Laboratory of Neurochemical Pharmacology, Institute of PharmacologyAcademy of Medical Sciences of the USSRMoscowRussia

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