Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia (original) (raw)

• Ackenheil M, Beckmann H, Greil W, Hoffmann G, Markianos E, Raese J (1974) Antipsychotic efficacy of clozapine in correlation to changes in catecholamine metabolism in man. Adv Biochem Psychopharmacol 9:647–658
  Google Scholar
• Ackenheil M, Blatt B, Lampart C (1975) Effect of clozapine on 5-HIAA excretion in urine and CSF of psychotic patients and on serotonin metabolism in rat brain. Acta Vitaminol Enzymol 29:79
  Google Scholar
• Altar CA, Wasley AM, Neale RF, Stone GA (1986) Typical and atypical anti-psychotic occupancy of D2 and S2 receptors: an autoradiographic analysis in rat brain. Brain Res Bull 16:517–525
  Google Scholar
• Altar CA, Boyar WC, Wasley A, Gerhardt SG, Liebman JM, Wood WL (1988) Dopamine neurochemical profile of atypical antipsychotics resembles that of D-1 antagonists. Naunyn-Schmiedeberg's Arch Pharmacol 338:162–168
  Google Scholar
• Andén NE, Stock G (1973) Effect of clozapine on the turnover of dopamine in the corpus striatum and in the limbic system. J Pharm Pharmacol 25:346–348
  Google Scholar
• Andersen PH, Braestrup C (1986) Evidence for different states of the dopamine D-1 receptor: clozapine and fluperlapine may preferentially label an adenylate cyclase-coupled state of the D-1 receptor. J Neurochem 47:1830–1831
  Google Scholar
• Andersen PH, Nielsen EB, Gronvald FC, Braestrup C (1986) Some atypical neuroleptics inhibit [3H]SCH-23390 binding in vivo. Eur J Pharmacol 120:143–144
  Google Scholar
• Angst J, Bente D, Berner P, Heimann H, Helmchen H, Hippius H (1971) Das klinische Wirkungsbild von Clozapine (Untersuchung mit dem AMP-System). Pharmakopsychiatrie 4:200–211
  Google Scholar
• Bacopolous NG, Hattox SE, Roth RH (1979) 3,4-Dihydroxyphenylacetic acid and homovanillac acid in rat plasma: possible indications of central dopaminergic activity. Eur J Pharmacol 56:225–236
  Google Scholar
• Banki CM (1978) Alterations of cerebrospinal fluid 5-hydroxyindoleacetic acid, and total blood serotonin content during clozapine treatment. Psychopharmacology 56:195–198
  Google Scholar
• Bannon MJ, Roth RH (1983) Pharmacology of mesocortical dopamine neurons. Pharmacol Rev 35:53–68
  Google Scholar
• Bartholini G, Haefely W, Jalfre M, Keller HH, Pletscher A (1972) Effect of clozapine on cerebral catecholaminergic neurone systems. Br J Pharmacol 46:736–740
  Google Scholar
• Bennett JP, Enna SJ, Bylund D, Gillin JC, Wyatt RJ, Snyder SH (1979) Neurotransmitter receptors in frontal cortex of schizophrenics. Arch Gen Psychiatry 36:927–934
  Google Scholar
• Bersani G, Grispini A, Marini S, Pasini A, Valducci M, Ciani N (1986) Neuroleptic-induced extrapyramidal side effects: clinical perspectives with ritanserin (R55667), a new selective 5-HT2 receptor blocking agent. Curr Ther Res 40:492–498
  Google Scholar
• Berzewski H, Helmchen H, Hippius H, Hoffman H, Kanowski S (1969) Das klinische Wirkungspektrum eines neuen Dibenzdiazepin-Derivates. Arzneimittelforschung 19:496–498
  Google Scholar
• Bischoff S, Scatton B, Korf J (1979) Biochemical evidence for a transmitter role of dopamine in the rat hippocampus. Brain Res 165:161–165
  Google Scholar
• Bischoff S, Dooley DJ, Mogilnicka E, Krauss J, Delini-Stula A (1983) Sensitivity changes of neurotransmitter receptors in the rat hippocampal formation after adrenalectomy. In: Endroczy E, Angelucci L, Scapagnini U, de Wied D (eds) Neuropeptides and psychosomatic processes. Akademiai Kladó, Budapest, pp 417–424
  Google Scholar
• Bischoff S, Heinrich M, Krauss J, Sills MA, Williams M, Varsont A (1988) Interaction of the D1 receptor antagonist SCH 23390 with the central 5-HT system: radioligand binding studies, measurements of biochemical parameters and effects on L-5-HTP syndrome. J Recep Res 8:107–120
  Google Scholar
• Blaha CD, Lane RF (1987) Chronic treatment with classical and atypical antipsychotic drugs differentially decrease dopamine release in striatum and nucleus accumbens in vivo. Neurosci Lett 78:188–204
  Google Scholar
• Bleich A, Brown S, Kahn R, van Praag HM (1988) The role of serotonin in schizophrenia. Schizophr Bull 297–315
• Bogerts B, Meertz E, Schönfeldt-Bausch R (1985) Basal ganglia and limbic system pathology in schizophrenia. A morphometric study of brain volume and shrinkage. Arch Gen Psychiatry 42:784–791
  Google Scholar
• Burki HR, Ruch W, Asper H (1976) Effects of clozapine, thioridazine, perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat. Psychopharmacologia 41:27–33
  Google Scholar
• Carlsson A (1977) Does dopamine play a role in schizophrenia? Psychol Med 7:583–597
  Google Scholar
• Carlsson A (1988) The current status of the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 1:179–186
  Google Scholar
• Carlsson A, Lindquist M (1963) Effect of chlorpromazine or haloperidol on the formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol Toxicol 20:140–144
  Google Scholar
• Casey DE (1989) Clozapine: neuroleptic-induced EPS and tardive dyskinesia. Psychopharmacology (in press)
• Chiodo LA, Bunney BS (1983) Typical and atypical neuroleptics differential effects of chronic administration of the activity of A9 and A10 midbrain dopaminergic neurons. J Neurosci 3:1607–1619
  Google Scholar
• Chiodo LA, Bunney BS (1985) Possible mechanisms by which repeated clozapine administration differentially affects the activity of two subpopulations of midbrain dopamine neurons. J Neurosci 5:2539–2544
  Google Scholar
• Claghorn J, Honigfeld G, Abuzzahab FS, Wang R, Steinbock R, Tuason V, Klerman G (1987) The risks and benefits of clozapine versus chlorpromazine. J Clin Psychopharmacol 7:377–384
  Google Scholar
• Clark D, White FJ (1988) D1 dopamine receptor—the search for a function: a critical evaluation of the D1/D2 dopamine receptor classification and its functional implications. Synapse 1:347–388
  Google Scholar
• Crow TJ (1980) Molecular pathology of schizophrenia: more than one disease process? Br Med J 280:66–68
  Google Scholar
• Crow TJ, Cross AJ, Johnstone EC, Owen F, Owens DGC, Waddinton JL (1982) Abnormal involuntary movements in schizophrenia: are they related to the disease process or its treatment? Are they associated with changes in dopamine receptors? J Clin Psychopharmacol 2:336–340
  Google Scholar
• Davila R, Manero E, Zumarraga M, Andea I, Schwertzer JW, Friedhoff AJ (1988) Plasma homovanillic acid as a predictor of response to neuroleptics. Arch Gen Psychiatry 45:564–567
  Google Scholar
• Drescher K, Hetcy L (1988) Influence of antipsychotics and serotonin antagonists on presynaptic receptors modulating the release of serotonin in synaptosomes of the nucleus accumbens of rats. Neuropharmacology 27:31–36
  Google Scholar
• Ebinger G, Michotte Y, Herregodts P (1987) The significance of homovanillic acid and 3,4-dihydroxyphenylacetic acid concentrations in human lumbar cerebrospinal fluid. J Neurochemistry 48:1725–1729
  Google Scholar
• Elsworth JD, Leahy DJ, Roth RH, Redmond DE Jr (1987) Homovanillac acid concentrations in brain, CSF and plasma as indicators of central dopamine function in primates. J Neural Transm 68:51–62
  Google Scholar
• Farde L, Wiesel F-A, Halldin C, Sedvall G (1988) Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs. Arch Gen Psychiatry 45:71–76
  Google Scholar
• Farde L, Wiesel F, Nordstrom A-L, Sedvall G (1989) D-1 and D-2-dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacology (in press)
• Faunt JE, Crocker AD (1988) Adrenocortical hormone status affects responses to dopamine receptor agonists. Eur J Pharmacol 152:255–261
  Google Scholar
• Fernstrom JD, Wurtman RJ (1972) Brain serotonin content: physiological regulation by plasma neutral amino acids. Science 178:414–416
  Google Scholar
• Fink H, Morgenstern R, Oelssner W (1984) Clozapine—a serotonin antagonist? Pharmacol Biochem Behav 20:513–517
  Google Scholar
• Friedman RL, Sanders-Bush E, Barrett RL (1985) Clozapine blocks disruptive and discriminative stimulus effects of quipazine. Eur J Pharmacol 106:191–193
  Google Scholar
• Gerlach J, Thorsen K, Fog R (1975) Extrapyramidal reactions and amine metabolites in cerebrospinal fluid during haloperidol and clozapine treatment of schizophrenic patient. Psychopharmacologica 40:341–350
  Google Scholar
• Gudelsky GA, Meltzer HY (1989) Activation of tuberoinfundibular dopamine neurons following the acute administration of atypical antipsychotics. Neuropsychopharmacology (in press)
• Gudelsky GA, Nash JF, Koenig JI, Meltzer HY (1987) Neuroendocrine effects of typical and atypical antipsychotics in the rat. Psychopharmacol Bull 23:483–486
  Google Scholar
• Harris PQ, Brown SJ, Friedman MJ, Bacopoulos NG (1984) Plasma drug and homovanillac acid levels in psychotic patients receiving neuroleptics. Biol Psychiatry 19:849–860
  Google Scholar
• Honigfeld G, Patin J, Singer J (1984) Clozapine: antipsychotic activity in treatment-resistant schizophrenics. Adv i Ther 1:77–97
  Google Scholar
• Imperato A, Angelucci L (1988) Effects of the atypical neuroleptics clozapine and fluperlapine on the in vivo dopamine release in the dorsal striatum and in the prefrontal cortex. Psychopharmacology [Suppl 1] 96:79
  Google Scholar
• Juul Povlsen VJ, Noring V, Fog R, Gerlach J (1985) Tolerability and therapeutic effect of clozapine: a retrospective investigations of 216 patients treated with clozapine for up to 12 years. Acta Psychiatr Scand 71:176–185
  Google Scholar
• Kane J, Honigfeld G, Singer J, Meltzer H (1988) Clozapine for the treatment-resistant schizophrenic: a double-blind comparison versus chlorpromazine/benztropine. Arch Gen Psychiatry 45:789–796
  Google Scholar
• Kebabian JW, Calne DB (1979) Multiple receptors for dopamine. Nature 277:93–96
  Google Scholar
• Koenig JI, Gudelsky GA, Meltzer HY (1987) Stimulation of corticosterone and β-endorphin secretion by selective 5-HT receptor subtype activation. Eur J Pharmacol 137:1–8
  Google Scholar
• Kostowski W, Gumulka W, Czlonkowski A (1972) Reduced cataleptogenic effects of some neuroleptics in rats with lesioned midbrain raphe and treated with p-chlorophenylalanine. Brain Res 48:443–446
  Google Scholar
• Koyama T, Meltzer HY (1986) A biochemical and neuroendocrine study of the serotonergic system in depression. In: Hippius H, Klerman GL, Mattussek N (eds) New results in depression. Springer, Berlin Heidelberg New York Tokyo, pp 169–188
  Google Scholar
• Kraepelin E (1919; reprinted 1971) Dementia praecos and paraphrenia. Krieger, Huntington, NY, p 83
  Google Scholar
• Kuha S, Miettinen E (1986) Long-term effect of clozapine in schizophrenia: a retrospective study of 108 chronic schizophrenics treated with clozapine for up to 7 years. Nord Psychiatr Tidskr 40:225–230
  Google Scholar
• Lai H, Carino MA, Houta H (1980) Antiserotonin properties of neuroleptic drugs. In: Yamamura HY, Olsen RW (eds) Psychopharmacology and biochemistry of neurotransmitter receptors. Elsevier, New York, pp 347–353
  Google Scholar
• Lee T, Tang SW (1984) Loxapine and clozapine decrease serotonin (S2) but do not elevate dopamine (D2) receptor numbers in the rat brain. Psychiatry Res 12:277–285
  Google Scholar
• Lee T, Seeman P, Tourtellotte WW, Farley IJ, Horneykeiwicz O (1978) Binding of 3H-neuroleptics and 3H-apomorphine in schizophrenic brains. Nature 274:897–900
  Google Scholar
• Lindström LH (1988) The effect of long term treatment with clozapine in schizophrenia: a retrospective study in 96 patients treated with clozapine for up to 13 years. Acta Psychiatr Scand 77:524–529
  Google Scholar
• Lowy MT, Koenig JI, Meltzer HY (1988) Stimulation of serum cortisol and prolactin in man by MK-212, a centrally active serotonin agonist. Biol Psychiatry 23:818–828
  Google Scholar
• Maas JW, Contreias SA, Bowden CL, Weintraub SE (1985) Effects of debrisoquin on CSF and plasma HVA concentration in man. Life Sci 36:2163–2170
  Google Scholar
• Mackay AVP (1980) Positive and negative schizophrenic symptoms and the role of dopamine. Br J Psychiatry 137:379–383
  Google Scholar
• Mackay AVP, Iversen LL, Rossor M, Spokes E, Bud E, Arrequi A, Creese I, Snyder S (1982) Increased brain dopamine and dopamine receptors in schizophrenia. Arch Gen Psychiatry 39:991–997
  Google Scholar
• Maj J, Sowinska H, Boran L, Palider W (1974) The central action of clozapine. Pol J Pharmacol Pharm 26:425–435
  Google Scholar
• Marder SR, Van Putten T (1988) Who should receive clozapine? Arch Gen Psychiatry 45:865–867
  Google Scholar
• Matsubara S, Meltzer HY (1989) Acute effects of neuroleptics on 5-HT2 receptor density in rat cerebral cortex. Life Sci (in press)
• Matz R, Rick W, Oh D, Thompson H, Gershon S (1954) Clozapine, a potential antipsychotic agent without extrapyramidal manifestations. Curr Ther Res 16:687–695
  Google Scholar
• McEwen BS (1987) Glucocorticoid-biogenic amine interactions in relation to mood and behavior. Biochem Pharmacol 36:1755–1763
  Google Scholar
• McQuade RD, Ford D, Duffy RA, Chipkin RE, Iorio LC, Barnett A (1988) Serotonergic component of SCH-23390: in vitro and in vivo binding analyses. Life Sci 43:1861–1866
  Google Scholar
• Meltzer HY (1976) Neuromuscular dysfunction in schizophrenia. Schizophren Bull 2:106–135
  Google Scholar
• Meltzer HY (1985) Dopamine and negative symptoms in schizophrenia: critique of the Type I-Type II hypothesis. In: Alpert M (ed) Controversies in schizophrenia: changes and constancies. Guilford Press, New York, pp 110–136
  Google Scholar
• Meltzer HY (1988) New insights into schizophrenia through atypical antipsychotic drugs. Comments on “the current status of the dopamine hypothesis of schizophrenia”. Neuropsychopharmacology 3:193–196
  Google Scholar
• Meltzer HY (1989a) Clozapine: clinical advantages and biological mechanisms. In: Schulz C, Tamminga C (eds) Schizophrenia: a scientific focus. Oxford Press, New York (in press)
  Google Scholar
• Meltzer HY (1989b) Clozapine: mechanism of action in relation to its clinical advantages. In: Kales A, Stefanos CN, Talbott JA (eds) Recent advances in schizophrenia. Springer, Heidelberg New York Tokyo
  Google Scholar
• Meltzer HY, Fang VS (1976) The effect of neuroleptics on serum prolactin in schizophrenic patients. Arch Gen Psychiatry 33:279–286
  Google Scholar
• Meltzer HY, Lowy MT (1987) The serotonin hypothesis of depression. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 513–526
  Google Scholar
• Meltzer HY, Luchins DJ (1984) Effect of clozapine in severe tardive dyskinesia: A case report. J Clin Psychopharmacology 4:316–322
  Google Scholar
• Meltzer HY, Stahl SM (1976) The dopamine hypothesis of schizophrenia: a review. Schizophren Bull 2:19–76
  Google Scholar
• Meltzer HY, Daniels S, Fang VS (1975) Clozapine increases rat serum prolactin levels. Life Sci 17:339–342
  Google Scholar
• Meltzer HY, Goode DJ, Schyve PM, Young M, Fang VS (1979) Effect of clozapine on human serum prolactin levels. Am J Psychiatry 136:1550–1555
  Google Scholar
• Meltzer HY, Busch DA, Fang VS (1984a) Neuroendocrine abnormalities in schizophrenia: prolactin, growth hormone and gonadrotrophins. In: Brown GM, Koslow SH, Reichlin S (eds) Neuroendocrinology and psychiatric disorders. Raven Press, New York, pp 1–28
  Google Scholar
• Meltzer HY, Kolakowska T, Fang VS, Fogg L, Robertson A, Lewine R, Strahilevitz M, Busch D (1984b) Growth hormone and prolactin response to apomorphine in schizophrenia and the major affective disorders: relation to duration of illness and depressive symptoms. Arch Gen Psychiatry 41:512–519
  Google Scholar
• Meltzer HY, Bastani B, Kwon K, Ramirez L, Burnett S, Sharpe J (1989) A prospective study of clozapine in treatment resistant schizophrenic patients: I: Preliminary Report. Psychopharmacology (in press)
• Mita T, Hanada S, Nishino N, Kuno T, Nakai H, Yamadori T, Mizoi Y, Tanaka C (1986) Decreased serotonin S2 and increased dopamine D2 receptors in chronic schizophrenics. Biol Psychiatry 21:1407–1414
  Google Scholar
• Nau NPV, Lal S, Cervantes P, Yassa R, Guyda H (1979) Effect of clozapine on apomorphine-induced growth hormone secretion and serum prolactin concentrations in schizophrenia. Neuropsychobiology 5:136–142
  Google Scholar
• Nash JF, Meltzer HY, Gudelsky GA (1988) Antagonism of serotonin receptor mediated neuroendocrine and temperature responses by atypical neuroleptics in the rat. Eur J Pharmacol 151:463–469
  Google Scholar
• Owen F, Cross AJ, Crow TJ, Longden A, Poulter M, Riley GJ (1978) Increased dopamine receptor sensitivity in schizophrenia. Lancet II 233–235
  Google Scholar
• Pickar D, Labarca R, Doran AR, Wolkowitz OM, Roy A, Breier A, Linnoila M, Paul SM (1986) Longitudinal measurement of plasma homovanillac acid levels in schizophrenic patients: correlation with psychosis and response to neuroleptic treatment. Arch Gen Psychiatry 43:669–676
  Google Scholar
• Pickar D, Labarca R, Linnoila M, Roy A, Hommer D, Everett D, Paul SM (1984) Neuroleptic-induced decrease in plasma homovanillac acid and antipsychotic activity in schizophrenic patients. Science 225:954–957
  Google Scholar
• Potkin SG, Cannon-Spoor E, DeLisi LE, Neckers IM, Wyatt RJ (1982) Plasma phenylalanine tyrosine, and tryptophan in schizophrenia. Arch Gen Psychiatry 40:749–752
  Google Scholar
• Rasmussen K, Aghajanian GK (1988) Potency of antipsychotics in reversing the effects of a hallucinogenic drug on loeus coeruleus neurons correlates with 5-HT2 binding affinity. Neuropsychopharmacology 1:101–107
  Google Scholar
• Reynolds GP, Rossor MN, Iversen LL (1983) Preliminary studies of human cortical 5-HT2 receptors and their involvement in schizophrenia and neuroleptic drug action. J Neural Transm [Suppl] 18:273–277
  Google Scholar
• Ruch W, Asper H, Bürki HR (1976) Effect of clozapine on the metabolism of serotonin in rat brain. Psychopharmacologia 46:103–109
  Google Scholar
• Sapolsky RM (1985) A mechanism for glucocorticoid toxicity in the hippocampus: increased neuronal vulnerability to metabolic insults. J Neurosci 5:1228–1232
  Google Scholar
• Schechter MD, Greer NL (1987) Evidence that the stimulus properties of apomorphine are mediated by both D1 and D2 receptor activation. Life Sci 40:2461–2471
  Google Scholar
• Seeman P, Bzowez NH, Guan HC, Bergeron C, Reynolds GP, Bud ED, Riederer P, Jellenger K, Towitellotte WW (1987) Human brain D1 and D2 dopamine receptors in schizophrenia, Alzheimer's, Parkinson's and Huntington's diseases. Neuropsychopharmacology 1:5–15
  Google Scholar
• Souto M, Monti JM, Althier H (1979) Effect of clozapine on the activity of central dopaminergic and noradrenergic neurons. Pharmacol Biochem Behav 10:5–9
  Google Scholar
• Stahl SM, Wets K (1987) Indoleamines and schizophrenia. In: Henn FA, DeLisi LE (eds) Handbook of schizophrenia 2. Neurochem Neuropharm of Schizophrenia, pp 257–296
• Waldmeir PC, Maitre L (1976) On the relevance of preferential increases of mesolimbic versus striatal dopamine turnover for the prediction of antipsychotic activity of psychotropic drugs. J Neurochem 27:589–587
  Google Scholar
• Whitaker PM, Crow TJ, Ferrier N (1981) Tritated LSD binding in frontal cortex in schizophrenia. Arch Gen Psychiatry 38:278–280
  Google Scholar
• White FJ, Wang RY (1983) Differential effects of classical and atypical antipsychotic drugs on A9 and A10 dopamine cells. Science 221:1054–1057
  Google Scholar
• Zemlan FP, Hirschowitz J, Garver DL (1986) Relation of clinical symptoms to apomorphine-stimulated growth hormone release in mood-incongruent psychotic patients. Arch Gen Psychiatry 43:1162–1167
  Google Scholar