Summary
The extent and duration of striatal dopamine-D2 receptor occupancy by savoxepine in humans has been studied using positron emission tomography with [11C]-raclopride, in order to investigate why the anticipated favourable ratio between its extrapyramidal and antipsychotic effects was not achieved in practice.
After 0.25 mg savoxepine, striatal D2 receptor occupancy peaked at 50–60% after 24–36 h and disappeared within 6 days. After doses of 0.1 mg to 0.5 mg, D2 receptor occupancy in the putamen and caudate nucleus increased from 20 to 70% 3–7 h after administration and amounted to 40 to 75% at the peak time (20–29 h).
This suggests that cumulative D2 receptor blockade would occur if equal or increasing doses of savoxepine were given repeatedly. Extrapyramidal adverse-effects would be likely to occur under such circumstances. An adequate test of the theory that preference for hippocampal dopamine D2 receptors with afford a good therapeutic ratio requires an alternative dosing regimen.
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Leenders, K.L., Antonini, A., Thomann, R. et al. Savoxepine: striatal dopamine-D2 receptor occupancy in human volunteers measured using positron emission tomography (PET). Eur J Clin Pharmacol 44, 135–140 (1993). https://doi.org/10.1007/BF00315470
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DOI: https://doi.org/10.1007/BF00315470