Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-06T00:21:48.677Z Has data issue: false hasContentIssue false
  • English
  • Français

Clozapine versus Perphenazine: The Value of the Biochemical Mode of Action of Neuroleptics in Predicting their Therapeutic Activity

Published online by Cambridge University Press:  29 January 2018

H. M. van Praag ,
J. Korf  and
L. C. W. Dols
H. M. van Praag
Affiliation:
Department of Biological Psychiatry, Psychiatric University Clinic, Oostersingel 59, Groningen, The Netherlands
J. Korf
Affiliation:
Department of Biological Psychiatry, Psychiatric University Clinic, Oostersingel 59, Groningen, The Netherlands
L. C. W. Dols
Affiliation:
Department of Biological Psychiatry, Psychiatric University Clinic, Oostersingel 59, Groningen, The Netherlands
Get access Rights & Permissions [Opens in a new window]

Summary

The chemical structure of a neuroleptic does not reliably predict the exact profile of its therapeutic action. We considered the question whether the biochemical action of a neuroleptic, and specifically the ratio between DA-receptor block and NA-receptor block, might have a higher predictive value in this respect. In this context we carried out a double-blind study of the therapeutic value of clozapine and perphenazine in acute psychoses of varying symptomatology and aetiology. There are strong indications that clozapine has only a slight inhibitory effect on transmission in central DA-ergic neurons, but markedly inhibits transmission in central NA-ergic neurons, and that the reverse applies to perphenazine. In view of these data we expected perphenazine to be a stronger antipsychotic and a weaker sedative than clozapine, and vice versa. The plausibility of this hypothesis was demonstrated. Partly also on the basis of earlier research, we concluded that the biochemical action of a neuroleptic is a more faithful predictor of its therapeutic action profile than the chemical structure.

Type
Papers
Information
The British Journal of Psychiatry , Volume 129 , Issue 6 , December 1976 , pp. 547 - 555
Copyright
Copyright © Royal College of Psychiatrists, 1976 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

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. Advanc. Biochem. Psychopharmacol., 9, 647–57.Google Scholar
Andén, N. E., Butcher, S. G., Corrodi, H., Fuxe, K. & Ungerstedt, U. (1970) Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Europ. J. Pharmacol., 11, 303–14.Google Scholar
Andén, N. E. & Stock, G. (1973) Effect of clozapine on the turnover of dopamine in the corpus striatum and in the limbic system. J. Pharm. Pharmacol., 25, 346–8.Google Scholar
Angst, J., Bente, D., Berner, P., Heimann, H., Helmchen, H. & Hippius, H. (1971a) Das klinische Wirkungsbild von Clozapin: Untersuchung mit dem AMP-System. Pkarmakopsychiat., 4, 200–11.Google Scholar
Angst, J. Jaenicke, U., Padrutt, A. & Scharfetter, Ch. (1971b) Ergebnisse eines Doppelblindversuchs von Clozapin (8-Chlor-11-(4-methyl-1-piperazinyl)-5 H-dibenzo (b,e) (1,4) diazepin) im Vergleich zu Levomepromazin. Pharmakopsychiat., 4, 192–200.Google Scholar
Bartholini, G., Haefely, W., Jalfre, M., Keller, H. H. & Pletscher, A. (1972) Effects of clozapine on cerebral catecholaminergic neurone systems. Brit. J. Pharmacol., 46, 736–40.Google Scholar
Bartholini, G. Keller, H. H. & Pletscher, A. (1973) Effect of neuroleptics on endogenous norepinephrine in rat brain. Neuropharmacology, 12, 751–6.Google Scholar
Bürki, H. R., Ruch, W., Asper, H., Baggiolini, M. & Stille, G. (1974) Effect of single and repeated administration of clozapine on the metabolism of dopamine and noradrenaline in the brain of the rat. Europ. J. Pharmacol., 27, 180–90.Google Scholar
Bürki, H. R., Ruch, W., Asper, H. (1975a) Effects of clozapine, thioridazine, perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat. Psychopharmacologia (Berl.), 41, 27–33.Google Scholar
Bürki, H. R. Eichenberger, E., Sayers, A. C. & White, T. G. (1975b) Clozapine and the dopamine hypothesis of schizophrenia, a critical appraisal. Pharmakopsychiat., 8, 115–21.Google Scholar
Buus Lassen, J. (1975) Evidence for noradrenaline (NA)—and dopamine (DA)—receptor blockade by clozapine. In Neuropharmacology (eds. Boisier, J. R., Hippius, H. and Pichot P.). Amsterdam-New York: Excerpta Medica.Google Scholar
Clement-Cormier, Y. C., Kebabian, J. W., Petzold, G. L. & Greengard, P. (1974) Dopamine-sensitive adenylate cyclase in mammalian brain: a possible site of action of antipsychotic drugs. Proc. Nat. Acad. Sci. U.S.A., 71, 1113–17.CrossRefGoogle Scholar
Costall, B. & Naylor, R. J. (1975) Detection of the neuroleptic properties of clozapine, sulpiride and thioridazine. Psychopharmacologia (Berl.), 43, 69–74.Google Scholar
Crow, T. J. & Gillbe, C. (1973) Dopamine antagonism and antischizophrenic potency of neuroleptic drugs. Nature New Biology, 245, 27–8.Google Scholar
Gerlach, J., Koppelhus, P., Helweg, E. & Monrad, A. (1974) Clozapine and haloperidol in a single-blind cross-over trial: therapeutic and biochemical aspects in the treatment of schizophrenia. Acta psychiat. Scand., 50, 410–24.Google Scholar
Griffith, R. W. & Saameli, K. (1975) Clozapine and agranulocytosis. Lancet, iv, 657.Google Scholar
Gross, H., Hackl, H. & Kaltenbaeck, E. (1970) Results of double-blind study of clozapine and thioridazine. VII CINP Congress, Prague.Google Scholar
Horn, A. S. & Phillipson, O. T. (1975) Noradrenalinesensitive adenylate cyclase in rat limbic forebrain homogenates: effects of agonists and antagonists. Brit. J. Pharmacol., 55, 299–300.Google Scholar
Iversen, L. L. (1975) Dopamine receptors in the brain. Science, 188, 1084–9.CrossRefGoogle ScholarPubMed
Jonge, H. de (1964) Inleiding tot de medische statistick. Verhandeling van het Nederlands Instituut voor Praeventieve Geneeskunde (Leiden).Google Scholar
Karobath, M. & Leitich, H. (1974) Antipsychotic drugs and dopamine-stimulated adenylate cyclase prepared from corpus striatum of rat brain. Proc. Nat. Acad. Sci. U.S.A., 71, 2915–18.Google Scholar
Keller, H. H., Bartholini, G. & Pletscher, A. (1973) Increase of 3-methoxy-4-hydroxyphenylethylene glycol in rat brain by neuroleptic drugs. Europ. J. Pharmacol., 23, 183–6.Google Scholar
Korf, J. & Praag, H. M. van (1971) Amine metabolism in the human brain: further evaluation of the probenecid test. Brain Res., 35, 221–30.Google Scholar
Korf, J. Schutte, H. H. & Venema, K. (1973) A semiautomated fluorometric determination of 5-hydroxyindoles in the nanogram range. Analyt. Biochem., 53, 146–53.Google Scholar
Lowe, G. R. (1973) The phenomenology of hallucinations as an aid to differential diagnosis. Brit. J. Psychiat., 123, 621–33.Google Scholar
Nybäck, H. & Sedvall, G. (1970) Further studies on the accumulation and disappearance of catecholamines formed from tyrosine-14C in mouse brain. Effects of some phenothiazinc analogues. Europ. J. Pharmacol., 10, 193–205.Google Scholar
Post, R. M., Fink, E., Carpenter, W. T. & Goodwin, F. K. (1975) Cerebrospinal fluid amine metabolites in acute schizophrenia. Arch. gen. Psychiat., 32, 1063–9.Google Scholar
Praag, H. M. van (1975a) Neuroleptics as a guideline to biological research in psychotic disorders. Compr. Psychiat., 16, 7–22.CrossRefGoogle ScholarPubMed
Praag, H. Dols, L. C. W. & Schut, T. (1975b) Biochemical versus psychopathological action profile of neuroleptics: A comparative study of chlorpromazine and oxypertine in acute psychotic disorders. Compr. Psychiat., 16, 255–63.Google Scholar
Praag, H. & Korf, J. (1975c) Neuroleptics, catecholamines and psychoses: a study of their interrelations. Amer. J. Psychiat., 132, 593–7.Google Scholar
Praag, H. & Korf, J. (1975d) The importance of dopamine in the pathogenesis of psychosis and the action of antipsychotic (neuroleptic) drugs. Sixth International Congress of Pharmacology, Helsinki. In press.Google Scholar
Praag, H. (1976a) Depression and Schizophrenia. A Contribution on their Chemical Pathology. New York: Spectrum Publications.Google Scholar
Praag, H. (1976b) About the impossible concept of schizophrenia. Compr. Psychiat., 17, 481.Google Scholar
Praag, H. & Korf, J. (1976c) Importance of the dopamine metabolism for the clinical effects and side effects of neuroleptics. Amer. J. Psychiat. In press.Google Scholar
Snyder, S. H., Greenberg, D. & Yamamura, H. I. (1974) Antischizophrenic drugs and brain cholinergic receptors. Arch. gen. Psychiat., 31, 58–61.Google Scholar
Stille, G., Lauener, H. & Eichenberger, E. (1971) The pharmacology of 8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo (b,c) (1,4) diazepine (clozapine). Il Farmaco, 26, 603–25.Google Scholar
Westerink, B. H. C. & Korf, J. (1975a) Determination of nanogram amounts of homovanillic acid in the central nervous system with a rapid semiautomated fluorometric method. Biochem. Med., 12, 106–14.Google Scholar
Westerink, B. H. C. & Korf, J. (1975b) Influence of drugs on striatal and limbic homovanillic acid concentration in the rat brain. Europ. J. Pharmacol., 33, 31–40.Google Scholar
Wiesel, F. A. & Sedvall, G. (1975) Effect of antipsychotic drugs on homovanillic acid levels in striatum and olfactory tubercle of the rat. Europ. J. Pharmacol., 30, 364–7.CrossRefGoogle ScholarPubMed
Zivkovic, B., Guidotti, A., Revuelta, A. & 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.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.