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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 286 (1974), S. 165-179 
    ISSN: 1432-1912
    Keywords: Lipidosis ; Antidepressants ; Neuroleptics ; Lymphocytes ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Lymphocytes of rat lymph nodes have previously been revealed as reliable and sensitive indicators of a particular drug side effect, notably a generalized phospholipidosis, inducible by a compound of amphiphilic character (chlorphentermine). The purpose of the present study was to examine the effects of other amphiphilic compounds upon rat lymphocytes. After oral administration of various tricyclic antidepressants (iprindole, imipramine, clomipramine, 1-chloro-amitriptyline, 1-chloro-10,11-dehydro-amitriptyline, noxiptiline, amitriptyline), or of two neuroleptic drugs (chlorpromazine, thioridazine) to rats, the popliteal lymph nodes were examined with the electron microscope. After a single application of either iprindole (50 mg/kg), imipramine (100 mg/kg), or clomipramine (150 mg/kg) small proportions of lymphocytes were found to contain abnormal lamellated cytoplasmic inclusions. The size and number of inclusions and the number of affected lymphocytes increased with further treatment. Similar observations were made after treatment with the chlorinated amitriptyline derivatives. On the other hand, only small numbers of lymphocytes were affected by noxiptiline, amitriptyline, chlorpromazine and thioridazine, even after prolonged treatments (up to 13 weeks) with high doses (up to 125–175 mg/kg). The present ultrastructural finding are interpreted as representing lipidosislike cellular alterations, yet of highly varying degrees. The large quantitative differences are tentatively suggested to be due to differences in the rate and mode of metabolism of the drugs, and due to differing degrees of amphiphilia of the compounds applied.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 52 (1980), S. 179-187 
    ISSN: 1432-0533
    Keywords: Medulla oblongata ; Rat ; Chlorophentermine ; Chloroquine ; Lipidosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study is concerned with the question of whether or not amphiphilic drugs (chloroquine, quinacrine, perhexiline) that fail to induce general lipidosis in the central nervous system (CNS) of adult rats can produce lipidosis in a circumventricular organ (area postrema) not furnished with a blood-brain barrier. Chlorphentermine known to induce general lipidosis in CNS of adult rats served as reference compound. All drugs, when chronically applied in high oral doses, induced significant perikaryal lipidosis in the area postrema. In the adjacent nuclei (nucleus tractus solitarii, nucleus dorsalis nervi vagi, nucleus nervi hypoglossi, nucleus gracilis), only chlorphentermine caused generalized lipidosis, whereas the other drugs had either limited or no effects. The present findings strongly suggest that the exemption, of most regions of the CNS of adult rats, from lipidosis induced by chloroquine and others is due to hindered drug distribution across the blood-brain barrier, rather than being due to non-susceptibility of central neurons toward the lipidosis-inducing action of the drugs.
    Type of Medium: Electronic Resource
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