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Long-term effect of perphenazine on the substantia nigra in rats

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A controlled blind study was made of the long-term effect of perphenazine enanthate (3.4 mg/kg/14 days for 12 months and 40 mg/kg/14 days for 6 months) upon the number of nerve cells (light microscopy) and the uptake of 3H-uridine (autoradiography) in the substantia nigra of rats. No significant differences were found between the numbers of nerve cells in treated and untreated animals, neither in the pars compacta nor in the pars reticularis. Nor were any significant differences found with regard to cell cytology or uptake of 3H-uridine. On the basis of the present data and certain clinical and neuroanatomic studies of patients with persistent signs of encephalopathy following long-term neuroleptic treatment it is suggested that perphenazine and related neuroleptics may exert an irreversible neurotoxic effect on the cells in the nigro-striatal system, but that this effect is not manifest until an elevated sensitivity to neuroleptics is present, e.g. in the form of age phenomena and/or psychiatric disease processes.

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Gerlach, J. Long-term effect of perphenazine on the substantia nigra in rats. Psychopharmacologia 45, 51–54 (1975). https://doi.org/10.1007/BF00426209

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Key words

  • Perphenazine enanthate
  • Substantia nigra
  • 3H-Uridine
  • Tardive dyskinesia