Lipidosis-like ultrastructural alterations in rat lymph nodes after treatment with tricyclic antidepressants or neuroleptics.

Abstract

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.