Search results for "Desmethylclozapine"
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Distribution of clozapine and desmethylclozapine between blood and brain in rats.
1999
Desmethylclozapine is the major metabolite of clozapine in serum. Although the metabolite is pharmacologically active in vitro, the occurrence of desmethylclozapine in brain under steady-state conditions and its role for clinical actions of clozapine are unclear. In this study 20 male Sprague-Dawley rats received five oral doses of clozapine 20 mg/kg at 1.5-h intervals. At 0.5, 1, 2 and 5 h after the last administration, at a time four animals were killed for analysis of clozapine and desmethylclozapine concentrations in serum and brain. The treatment yielded steady-state serum concentrations of clozapine that are considered as therapeutically effective in man. Desmethylclozapine concentrat…
Effects of clozapine metabolites and chronic clozapine treatment on rat brain GABAA receptors
1996
Abstract Similarly to clozapine, a clozapine metabolite, N -desmethylclozapine, but not clozapine N -oxide, antagonized brain γ-aminobutyric acid type A (GABA A ) receptors at high micromolar concentrations. However, daily subcutaneous injections of clozapine (10 and 25 mg/kg) and haloperidol (0.5 mg/kg) for 14 days failed to alter the modulation by GABA of rat cerebrocortical and cerebellar benzodiazepine ([ 3 H]flunitrazepam) or convulsant ( t -[ 35 S]bicyclophosphorothionate) binding sites of the GABA A receptor. The results thus suggest that the GABA A receptor antagonism exerted by chronic in vivo clozapine treatment is weak as compared to this treatment's actions on certain monoamine …