Abstract
Urinary MHPG excretion in patients with acute schizophrenia was studied before and during a trial of the isomers of flupenthixol and placebo. Pretrial MHPG excretion was not related to severity of illness before the trial or to other pretrial clinical variables. In male subjects higher pretrial MHPG excretion was associated with a better outcome 1 year post-trial. However in females no relationship between MHPG excretion and outcome was established. During the trial there was a reduction in MHPG excretion in patients treated with β-flupenthixol but no decrease in the group treated with α-flupenthixol or chlorpromazine. In patients on placebo there was a reduction in MHPG excretion in those who dit well clinically, but not in those who did poorly. Thus low MHPG excretion may be a predictor of poor outcome in schizophrenia, but MHPG excretion also changes both as a function of clinical state and of neuroleptic drug administration.
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Andén, N. E., Butcher, S. G., Corrodi, H., Fuxe, K., Ungerstedt, U.: Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Eur. J. Pharmacol. 11, 303–314 (1970)
Atsmon, A., Blum, I., Steiner, M., Letz, A., Wijsenboek, H.: Further studies with propranolol in psychotic patients: Relation to initial psychiatric state, urinary catecholamines and 3-methoxy-4-hydroxyphenylglycol excretion. Psychopharmacology 27, 249–254 (1972)
Baillie, T. A., Boobis, A. R., Davies, D. S., Jones, D. H., Murray, S., Reid, J. L.: Studies on the metabolic fate of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) in man. Br. J. Pharmacol. 60, p. 280 (1977)
Berridge, T. L., Sharman, D. F.: The effect of tranquillizing drugs on the concentration of the sulphate ester of 4-hydroxy-3-methoxyphenylethane-1,2-diol in rat brain. Br. J. Pharmacol. 50, 156–158 (1974)
Bond, P. A., Dimitrakoudi, M., Howlett, D. R., Jenner, F. A.: Urinary excretion of the sulphate and glucuronide of 3-methoxy-4-hydroxyphenylethyleneglycol in a manic-depressive patient. Psychol. Med. 5, 279–285 (1975)
Bond, P. A., Howlett, D. R.: Measurements of the two conjugates of 3-methoxy-4-hydroxyphenylglycol in urine. Biochem. Med. 10, 219–228 (1974)
Bonsnes, R. W., Taussky, H. H.: The colorimetric determination of creatinine by the Jaffe reaction. J. Biol. Chem. 158, 581–591 (1945)
Carlsson, A.: Does dopamine play a role in schizophrenia? Psychol. Med. 7, 583–597 (1977)
Cooper, B.: Social class and prognosis in schizophrenia. Br. J. Prev. Soc. Med. 15, 17–41 (1961)
Corrodi, H., Fuxe, K., Lidbrink, P., Olsen, L.: Minor tranquillisers, stress and central catecholamine neurones. Brain Res. 29, 1–16 (1971)
Davis, K., Holister, L. E., Goodwin, F. K., Gordon, E. K.: Neurotransmitter metabolites in the cerebrospinal fluid of man following physostigmine. Life Sci. 21, 933–936 (1977)
Ebert, M. H., Kopin, I. J.: Differential labelling of origins of urinary catecholamine metabolites by dopamine — 14C. Trans. Assoc. Am. Physicians 88, 256–264 (1975)
Feighner, J. P., Robins, E., Guze, S. B., Woodruff, R. A., Winokur, G., Munoz, R.: Diagnostic criteria for use in psychiatric research. Arch. Gen. Psychiatry 26, 57–63 (1972)
Horn, A. S., Phillipson, O. T.: Noradrenaline sensitive adenylate cyclase in rat limbic forebrain homogenates: Effects of agonists and antagonists. Br. J. Pharmacol. 55, 299–300 (1975)
Howlett, D. R., Jenner, F. A.: Studies relating to the clinical significance of urinary 3-methoxy-4-hydroxyphenylethylene glycol. Br. J. Psychiatry 132, 49–54 (1978)
Johnstone, E. C., Crow, T. J., Frith, C. D., Carney, M. W. P., Price, J. S.: Mechanism of the antipsychotic effect in the treatment of acute schizophrenia. Lancet 1978I, 848–851
Joseph, M. H., Baker, H. F., Johnstone, E. C., Crow, T. J.: Determination of 3-methoxy-4-hydroxyphenylglycol conjugates in urine. Application to the study of central noradrenaline metabolism in unmedicated chronic schizophrenic patients. Psychopharmacology 51, 47–51 (1976)
Karoum, F., Moyer-Schwing, J., Potkin, S. G., Wyatt, R. J.: Presence of free, sulphate and glucuronide conjugated 3-methoxy-4-hydroxyphenylglycol (MHPG) in human brain, cerebrospinal fluid and plasma. Brain Res. 125, 333–339 (1977)
Kazič, T.: Norepinephrine synthesis and turnover in the brain: acceleration by physostigmine. In: Frontiers in catecholamine research, E. Usdin, S. H. Snyder, eds., pp. 897–899. New York: Pergamon 1973
Keller, H. H., Bartholini, G., Pletscher, A.: Increase of 3-methoxy-4-hydroxyphenylethylene glycol in rat brain by neuroleptic drugs. Eur. J. Pharmacol. 23, 183–186 (1973)
Krawiecka, M., Goldberg, D., Vaughan, M.: A standardised psychiatric assessment for rating chronic psychotic patients. Acta Psychiatr. Scand. 55, 299–308 (1977)
Mass, J. W.: Biogenic amines and depression. Arch. Gen. Psychiatry 32, 1357–1361 (1975)
Mass, J. W., Dekirmenjian, H., Fawcett, J. A.: MHPG excretion by patients with affective disorders. Int. Pharmacopsychiatry 9, 14–26 (1974)
Mass, J. W., Hattox, S. E., Landis, D. H., Roth, R. H.: A direct method for studying 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) production by brain in awake animals. Eur. J. Pharmacol. 46, 221–228 (1977)
Maas, J. W., Landis, D. H.: The metabolism of circulating norepinephrine by human subjects. J. Pharmacol. Exp. Ther. 177, 600–612 (1971)
Maas, J. W., Landis, H., Dekirmenjian, H.: The occurrence of free vs conjugated MHPG in non-human primate brain. Psychopharmacol. Commun. 2, 403–410 (1976)
Miller, R. J.: Comparison of the inhibitory effects of neuroleptic drugs on adenylate cyclase in rat tissue stimulated by dopamine, adrenaline and glucagon. Biochem. Pharmacol. 25, 537–541 (1976)
Moller-Nielsen, I., Pedersen, V., Nymark, K. F., Franck, V., Boeck, B., Fjallan, B., Christensen, A. V.: The comparative pharmacology of flupenthixol and some reference neuroleptics. Acta. Pharmacol. Toxicol. 33, 353–362 (1973)
Peroutka, S. J., U'Prichard, D. C., Greenberg, D. A., Snyder, S. H.: Neuroleptic drug interactions with norepinephrine alpha receptor binding sites in rat brain. Neuropharmacology 16, 549–556 (1977)
Riederer, P., Birkmayer, W., Seeman, D., Wutketich, S.: Brain noradrenaline and 3-methoxy-4-hydroxyphenylglycol in Parkinson's syndrome. J. Neural. Transm. 41, 241–251 (1977)
Skolnick, P., Daly, D. W., Freedman, R., Hoffer, B. J.: Interrelationships between catecholamine-stimulated formation of adenosine 3′, 5′-monophosphate in cerebellar slices and ïnhibitory effects on cerebellar purkinje cells: Antagonism by neuroleptic compounds. J. Pharmacol. Exp. Ther. 197, 280–292 (1976)
Swahn, C. G., Wiesel, F. A.: Determination of conjugated monoamine metabolites in brain tissue. J. Neural. Transm. 39, 281–290 (1976)
Taube, S. L., Kirstein, L. S., Sweeney, D. R., Heninger, G. R., Maas, J. W.: Urinary 3-methoxy-4-hydroxyphenylglycol and psychiatric diagnosis. Am. J. Psychiatry 135, 78–81 (1978)
Wing, J. K., Cooper, J. E., Sartorius, N.: The measurement and classification of psychiatric symptoms. London: Cambridge University Press 1973
Yorkston, N. J., Zaki, S. A., Pitcher, D. R., Gruzelier, J. H., Hollander, D., Serjeant, H. G. S.: Propranolol as an adjunct to the tratment of schizophrenia. Lancet 1977II, 575–578
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Joseph, M.H., Baker, H.F., Johnstone, E.C. et al. 3-Methoxy-4-hydroxyphenylglycol excretion in acutely schizophrenic patients during a controlled clinical trial of the isomers of flupenthixol. Psychopharmacology 64, 35–40 (1979). https://doi.org/10.1007/BF00427342
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DOI: https://doi.org/10.1007/BF00427342