Abstract
Agranulocytosis and the release of transaminase enzymes from liver cells are known consequences of neuroleptic drug use. These effects are most common with low potency neuroleptic drugs. It has been hypothesized that these effects are due to the direct toxic action of these drugs on blood and liver cells.
The purpose of this study is to compare the cytotoxic effects of eight neuroleptic drugs in five different biological test systems. In all of the test systems, thioridazine, chlorpromazine, trifluoperazine, fluphenazine and thiothixene (group one drugs) were the most toxic drugs and molindone was the least toxic. Thioridazine was between 25 and 84 times more toxic than molindone. Loxapine was significantly more toxic than molindone, but less toxic than the group one drugs. Haloperidol was intermediate in toxicity between the group one drugs and loxapine. We conclude that the difference in cytotoxicity of the neuroleptic drugs observed in these experiments accounts in part for the increase in agranulocytosis and hepatotoxicity with thioridazine and chlorpromazine and for the lower incidence of these side effects with less toxic drugs.
The possibility that tardive dyskinesia may be due to the cytotoxic effects of neuroleptic drugs is discussed and an experiment to test this hypothesis is suggested.
Similar content being viewed by others
References
Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Christensen E, Miller JE, Faurbye A (1970) Neuropathological investigation of 28 brains from patients with dyskinesia. Acta Psychiatr Scand 46:14–23
Clarke E (ed) (1978) Isolation and Identification of Drugs. The Pharmaceutical Press, London, England
Curry SH, Marshall JH, Davis JM (1970 b) Chlorpromazine plasma levels and effects. Arch Gen Psychiatry 22:289–296
Dujovne CA, Zimmerman HT (1969) Cytotoxicity of phenothiazines on Chang liver cells as measured by enzyme leakage. Proc Soc Exp Biol Med 131:583–587
Dulbecco R, Freeman G (1959) Plaque production by polyoma virus. Virology 8:396–397
Faurbye A (1970) The structural and biochemical basis of movement disorders in treatment with neuroleptic drugs. Comp Psychiatry 11:205–225
Forsman A, Ohman R (1976) Pharmacokenetic studies on haloperidol in man. Curr Ther Res 20:319–336
Galenberg AJ (1976) Computerized tomography in patients with tardive dyskinesia. Am J Psychiatry 133:578
Gee S, Mesard L (1979) Psychiatric drug study, Part I. Psychiatric Ward/Unit Study. Office of the Comptroller, Monograph No. 9 Washington DC, US Veterans Administration
Gottschalk LA, Biener R, Noble EP et al (1975) Thioridazine plasma levels and clinical response. Comp Psychiatry 16:323–337
Hollister LE (1978) Clinical pharmacology of psychotherapeutic drugs. New York, London. Churchill Livingstone 159:176–177
Hunter R, Blackwood W, Smith M, Cumings JN (1968) Neuropathological findings in three cases of persistant dyskinesia following phenothiazine medication. J Neurol Sci 7:263–273
Ishak KG, Irey NS (1972) Hepatic injury associated with the phenothiazines. Arch Pathol 93:283–304
Jeste DV, Potkin SG, Sinha S (1979) Tardive dyskinesia: Reversable and persistant. Arch Gen Psychiatry 36:585–590
Kane JM, Rifkin A, Woerner M, Reardon G, Sarantakos S, Schiebel P, Ramos-Lorenzi J (1983) Low dose neuroleptic treatment of our patient schizophrenics. ArchGen Psychiatry 40:893–896
Nielson EB, Lyon M (1978) Evidence for cell loss in corpus striatum after long term treatment with a neuroleptic drug flupenthixol in rats. Psychopharmacology 59:85–90
Oppenheim JJ, Schecter B (1976) Manual of clinical immunology. Rose NR, Friedman H (eds) American Society for Microbiology, Washington, DC, pp 81–94
Pandurangi AK, Devi V, Channabasavanna SM (1980) Caudate atrophy in irreversible tardive dyskinesia. J Clin Psychiatry 41:229–231
Perris C, Dimitrjevic P, Jacobsson L, Paulson P, Rapp W, Froberg H (1979) Tardive dyskinesia in psychiatric patients treated with neuroleptics. Br J Psychiatry 135:509–514
Phillips HJ (1973) Dye exclusion tests of cell viability. In: Krause PF, Patterson MD (eds) Tissue culture methods and applications. Academic Press, New York, pp 406–408
Pisciotta V (1973) Immune and toxic mechanisms in drug-induced agranulocytosis. Semin Hematol 10:279–305
Pisciotta V (1978) Drug induced agranulocytosis. Drugs 15:132–143
Reed LJ, Muench H (1938) A simple method of estimating fifty percent endpoints. Am J Hyg 27:493–497
Rovozzo GC, Burke CN (1973) A manual of basic virological techniques. Prentice-Hall, Englewood Cliffs, NJ, pp 16–37
Simpson GM, Varga E, Lee JH, et al. (1978) Tardive dyskinesia and psychotropic drug history. Psychopharmacology 58:117–124
Smith RC, Strizich M, Klaus D (1978) Drug history in tardive dyskinesia. Am J Psychiatry 135:1402–1403
Usdin E, Efron D (1972) Psychotropic drugs and related compounds. DHEW Publication No. (HSM) 72–9074, US Government Printing Office, Washington DC
Windholz M (ed) (1983) The Merck index tenth edition. Merck and Co, Inc. Rahway, NJ
Zimmerman HJ (1968) Spectrum of hepatotoxicity. Perspect Biol Med 12:135–161
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Munyon, W.H., Salo, R. & Briones, D.F. Cytotoxic effects of neuroleptic drugs. Psychopharmacology 91, 182–188 (1987). https://doi.org/10.1007/BF00217059
Issue Date:
DOI: https://doi.org/10.1007/BF00217059