Flunarizine induces a transient loss of tyrosine hydroxylase immunoreactivity in nigrostriatal neurons.
Neurotoxic effects of flunarizine (Fz), a selective calcium channel blocker, on the nigrostriatal dopamine system was investigated. Systemic injections of Fz to mice resulted in a transient loss of tyrosine hydroxylase (TH) immunoreactive nigrostriatal neurons without cell loss. TH immunoreactivity in these neurons was greatly reduced as rapidly as one day after drug administration (regardless of dosage used) and thereafter recovered in both dose- and time-dependent manners. Such a novel neurotoxic action of Fz may constitute a morphological substrate for reversible drug-induced parkinsonian signs described in recent clinical case reports.
Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis 38163.
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Takada
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Kono
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Kitai
D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D005444:Flunarizine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects* / Q000378:metabolism
D014446:Tyrosine 3-Monooxygenase; D005444:Flunarizine