A positron emission tomography (PET) study of cerebral dopamine D2 and serotonine 5-HT2A receptor occupancy in patients treated with cyamemazine (Tercian)

Rationale: Cyamemazine (Tercian) is an antipsychotic drug with anxiolytic properties. Recently, an in vitro study showed that cyamemazine possesses high affinity for serotonin 5-HT2A receptors, which was fourfold higher than its affinity for dopamine D-2 receptors ( Hameg et al. 2003). Objectives: The aim of this study is to confirm these previous data in vivo in patients treated with clinically relevant doses of Tercian. Methods: Eight patients received 37.5, 75, 150 or 300 mg/day of Tercian depending on their symptomatology. Dopamine D-2 and serotonin 5-HT2A receptor occupancies (RO) were assessed at steady-state plasma levels of cyamemazine with positron emission tomography ( PET), using [C-11] raclopride and [C-11] N-methyl-spiperone, respectively. The effective plasma level of the drug leading to 50% of receptor occupancy was estimated by fitting RO with plasma levels of cyamemazine at the time of the PET scan. Results: Cyamemazine induced near saturation of 5-HT2A receptors (RO = 62.1 - 98.2%) in the frontal cortex even at low plasma levels of the drug. On the contrary, occupancy of striatal D-2 receptors increased with plasma levels, and no saturation was obtained even at high plasma levels (RO = 25.2 - 74.9%). The effective plasma level of cyamemazine leading to 50% of D-2 receptor occupancy was fourfold higher than that for 5-HT2A receptors. Accordingly, individual 5-HT2A/D-2 RO ratios ranged from 1.26 to 2.68. No patients presented relevant increased prolactin levels, and only mild extrapyramidal side effects were noticed on Simpson and Angus Scale. Conclusion: This in vivo binding study conducted in patients confirms previous in vitro findings indicating that cyamemazine has a higher affinity for serotonin 5-HT2A receptors compared to dopamine D-2 receptors. In the dose range 37.5 - 300 mg, levels of dopamine D-2 occupancy remained below the level for motor side effects observed with typical antipsychotics and is likely to explain the low propensity of the drug to induce extrapyramidal side effects.