Psychopharmacologia

, Volume 40, Issue 4, pp 341–350 | Cite as

Extrapyramidal reactions and amine metabolites in cerebrospinal fluid during haloperidol and clozapine treatment of schizophrenic patients

  • J. Gerlach
  • K. Thorsen
  • R. Fog
Short Reports Human Pharmacology

Abstract

8 male schizophrenic patients participated in a double-blind, cross over study of the extrapyramidal side-effects of haloperidol and clozapine (acute dystonia, Parkinsonism and tardive dyskinesia), together with their effect on homo-vanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF). Haloperidol (9 mg/day) caused Parkinsonism, reduced tardive dyskinesias and increased the HVA concentration in the CSF. Clozapine (225 mg/day) had no effect on the neurological phenomena but reduced HVA and 5-HIAA concentrations in the CSF. During the discontinuation phase following the administration of haloperidol, tardive dyskinesia occurred or was aggravated; this did not occur after administration of clozapine. Accordingly, it is suggested that clozapine does not induce dopaminergic hypersensibility and, therefore, will not induce tardive dyskinesias.

Key words

Clozapine Haloperidol Parkinsonism Tardive Dyskinesia Homovanillic Acid Dopaminergic Hypersensitivity 5-Hydroxyindoleacetic Acid 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Andén, N.-E., Butcher, S. G., Corrodi, H., Fuxe, K., Ungerstedt, U.: Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Europ. J. Pharmacol. 11, 303–314 (1970)Google Scholar
  2. Andén, N.-E., Stock, G.: Effect of clozapine on the turnover of dopamine in the corpus striatum and in the limbic system. J. Pharm. Pharmacol. 25, 346–348 (1973)Google Scholar
  3. Angst, J.: Ergebnisse eines Doppelblindversuches von HF 1854 (8-Chlor-11-(4-methyl-1-piperazinyl)-5H-dibenzo (b,e) (1, 4) diazepin im Vergleich zu Levomepromazin. Pharmakopsychiat. 4, 192–200 (1971)Google Scholar
  4. Asper, H., Baggiolini, M., Bürki, H. R., Lauener, H., Ruch, W., Stille, G.: Tolerance phenomena with neuroleptics. Catalepsy apomorphine stereotypies and striatal dopamine metabolism in the rat after single and repeated administration of loxapine and haloperidol. Europ. J. Pharmacol. 22, 287–294 (1973)Google Scholar
  5. Ayd, F. J.: Persistent dyskinesia: a neurological complication of major tranquilizers. Med. Sci. 18, 32–40 (1967)Google Scholar
  6. Ayd, F. J.: Neuroleptics and antiparkinsonian drugs. Int. Drug. Ther. Newsletter 6, 33 (1971)Google Scholar
  7. Ayd, F. J.: Haloperidol: 15 years of clinical experience. Dis. nerv. Syst. 33, 459–469 (1972)Google Scholar
  8. Bartholini, G., Haefely, W., Jalfre, M., Keller, H. H., Pletscher, A.: Effects of clozapine on cerebral catecholaminergic neurone systems. Brit. J. Pharmacol. 46, 736–740 (1972)Google Scholar
  9. Bowers, M. B.: 5-Hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) following probenecid in acute psychotic patients treated with phenothiazines Psychopharmacologia (Berl.) 28, 309–318 (1973)Google Scholar
  10. Bürki, H. R., Ruch, W., Asper, H., Baggiolini, M., Stille, G.: Pharmakologische und neurochemische Wirkungen von Clozapin: neue Gesichtspunkte in der medikamentösen Behandlung der Schizophrenie. Schweiz, med. Wschr. 103, 1716–1724 (1973)Google Scholar
  11. Chase, T. N.: Central monoamine metabolism in man. Arch. Neurol. (Chic.) 29, 349–351 (1973)Google Scholar
  12. Chase, T. N., Schnur, J. A., Gordon, E. K.: Cerebrospinal fluid monoamine catabolites in drug-induced extrapyramidal disorders. Neuropharmacology 9, 265–268 (1970)Google Scholar
  13. Christensen, E., MØller, J. E., Faurbye, A.: Neuropathological investigations of 28 brains from patients with dyskinesia. Acta psychiat. scand. 46, 14–23 (1970)Google Scholar
  14. Crane, G. E.: Tardive dyskinesia in patients treated with major neuroleptics: A review of the literature. Amer. J. Psychiat. 124, 40–48 (1968)Google Scholar
  15. Crane, G. E.: Persistent dyskinesia. Brit. J. Psychiat. 122, 395–405 (1973)Google Scholar
  16. DiMascio, A., Demirgian, E.: Antiparkinson drug overuse. Psychosomatics 11, 596–601 (1970)Google Scholar
  17. Faurbye, A.: The structural and biochemical basis of movement disorders in treatment with neuroleptic drugs and in extrapyramidal diseases. Compr. Psychiat. 11, 205–225 (1970)Google Scholar
  18. Fischer-Cornelssen, K., Ferner, U., Steiner, H.: Multifokale Psychopharmakaprüfung. Arzneimittel-Forsch. (Drug Res.) 24, 1006–1007 (1974)Google Scholar
  19. Fjalland, B., MØller-Nielsen, I.: Enhancement of methylphenidate-induced stereotypies by repeated administration of neuroleptics. Psychopharmacologia (Berl.) 34, 105–109 (1974)Google Scholar
  20. Fog, R.: Neuroleptic action of clozapine injected into various brain areas in rats. J. Pharmacol. 5, suppl. 2, 32 (1974)Google Scholar
  21. Gerlach, J., Reisby, N., Randrup, A.: Dopaminergic hypersensitivity and cholinergic hypofunction in the pathophysiology of tardive dyskinesia. Psychopharmacologia (Berl.) 34, 21–35 (1974)Google Scholar
  22. Gerlach, J., Koppelhus, P., Helweg, E., Monrad, A.: Clozapine and haloperidol in a single-blind corss-over trial: Therapeutic and biochemical aspects in the treatment of schizophrenia. Acta psychiat. 50, 410–424 (1974)Google Scholar
  23. Hyttel, J.: Effect of neuroleptics on the disappearance rate of 3H-labelled catecholamines formed from 14C-tyramine in mouse brain. J. Pharm. Pharmacol. 26, 588–596 (1974)Google Scholar
  24. Kazamatsuri, H., Chien, C, Cole, J. O.: Treatment of tardive dyskinesia. II. Shortterm efficacy of dopamine-blocking agents haloperidol and thiopropazate. Arch. gen. Psychiat. 27, 100–103 (1972)Google Scholar
  25. Klawans, H. L.: The pharmacology of tardive dyskinesia. Amer. J. Psychiat. 130, 82–86 (1973)Google Scholar
  26. Pakkenberg, H., Fog, R., Nilakantan, B.: The long-term effects of perphenazine enanthate on the rat brain. Psychopharmacologia (Berl.) 29, 329–336 (1973)Google Scholar
  27. Papeschi, R.: Dopamine extrapyramidal system and psychomotor function. Psychiat. Neurol. Neurochir. (Amst.) 75, 13–48 (1972)Google Scholar
  28. Papeschi, R., McClure, D. J.: Homovanillic and 5-hydroxyindoleacetic acid in cerebrospinal fluid of depressed patients. Arch. gen. Psychiatry 25, 354–358 (1971)Google Scholar
  29. Post, R. M., Kotin, J., Hoodwin, F. K., Gordon, E. K.: Psychomotor activity and cerebrospinal fluid amine metabolites in affective illness. Amer. J. Psychiat. 130, 67–72 (1973)Google Scholar
  30. Sayers, A. C, Bürki, H., Ruch, W., Asper, H.: Hypersensitivity of striatal dopamine receptors in the rat. A method of predicting the occurrence of tardive dyskinesias after antipsychotic drugs. J. Pharmacol. 5, suppl. 2, 88 (1974)Google Scholar
  31. Schildkrut, R., Ackenheil, M., Eben, R. Raise, I., Rüther, E.: Effect of haloperidol treatment on metabolism of biogenic amines, extrapyramidal and psychopathological symptoms. J. Pharmacol. 5, suppl. 2, 90 (1974)Google Scholar
  32. Sedvall, G., NybÄck, H.: Effect of clozapine and some other antipsychotic agents on synthesis and turnover of dopamine formed from 14C-tyrosine in mouse brain. Israel J. med. Sci., suppl. to vol. 9, 24–30 (1973)Google Scholar
  33. Siegel, G. J., Mones, R. J.: Modification of choreiform activity by haloperidol. J. Amer. med. Ass. 216, 675–676 (1971)Google Scholar
  34. Sommer, H.: Die aktive psychiatrische Therapie unter Berücksichtigung tierexperimenteller Untersuchungen, pp. 58–78. Jena: VEB G. Fischer 1971Google Scholar
  35. Stawarz, F. J., Robinson, S., Sulser, F., Dingell, J. V.: On the significance of the increase of homovanillic acid (HVA) caused by antipsychotics in corpus striatum and limbic forebrain. Fed. Proc. 33, 246 (1974)Google Scholar
  36. Stille, G., Lauener, H., Eichenberger, E.: The pharmacology of 8-chloro-ll-(4-methyl-1-piperazinyl)-5H-dibenzo [b,e] [1,4] diazepine (clozapine). Farmaco, Ed. prat. 26, 603–625 (1971)Google Scholar

Copyright information

© Springer-Verlag 1975

Authors and Affiliations

  • J. Gerlach
    • 1
  • K. Thorsen
    • 1
  • R. Fog
    • 1
  1. 1.Dept. ESct. Hans HospitalRoskildeDenmark

Personalised recommendations