Pharmacopsychiatry 2003; 36 - 116
DOI: 10.1055/s-2003-825367

Transport of clozapine and its major metabolites into human cells of glial and neuronal origin

U Henning 1, K Krieger 1, S Loeffler 1, A Klimke 1
  • 1Neurobiochemical Research Unit, Department of Psychiatry, Heinrich-Heine-University Duesseldorf, Duesseldorf

Clozapine exerts superior efficacy in therapy-resistant schizophrenia. Its advantages as an atypical drug are counteracted by an induction of agranulocytosis. As shown (1), clozapine is actively transported into promyeloid leukemia cells.

To investigate clozapine transport into cells of brain origin with implication on cell vitality and function, we investigated the cellular accumulation of clozapine and its major metabolites by glioblastoma (86HG-39) and neuroblastoma (SH-SY5Y) cells using HPLC with electrochemical detection (2).

All cell lines showed an active transport which was saturable, energy and temperature dependent. Definite differences in the accumulation of clozapine and its metabolites were determined in respect to Vmax but less for Km. The rank order of drug transport was – beginning with the highest: norclozapine>clozapine>clozapine-N-oxid, indicating an accelerated uptake of the pharmacologically active metabolite norclozapine. Therefore the accumulation of clozapine besides specific receptor binding might have relevance for the molecular interactions of cells in vivo.

Henning, U. et al. Pharmacopsychiatry 35 (2002) 90–95;

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