title: Potential role of cortical 5-HT(2A) receptors in the anxiolytic action of cyamemazine in benzodiazepine withdrawal.
abstract: The antipsychotic cyamemazine is a potent serotonin 5-HT(2A) receptor (5-HT(2AR)) antagonist. A positron emission tomography (PET) study in human patients showed that therapeutic doses of cyamemazine produced near saturation of 5-HT(2AR) occupancy in the frontal cortex, whereas dopamine D(2) occupancy remained below the level for motor side effects observed with typical antipsychotics. Recently, numerous studies have revealed the involvement of 5-HT(2AR) in the pathophysiology of anxiety and a double-blind, randomized clinical trial showed similar efficacy of cyamemazine and bromazepam in reducing the anxiety associated with benzodiazepine withdrawal. Therefore, we reviewed the above articles about 5-HT(2AR) and anxiety in order to understand better the anxiolytic mechanisms of cyamemazine in benzodiazepine withdrawal. The 5-HT(2AR) is the most abundant serotonin receptor subtype in the cortex. Non-pharmacological studies with antisense oligodeoxynucleotides and genetically modified mice clearly showed that cortical 5-HT(2AR) signaling positively modulates anxiety-like behavior. With a few exceptions, most other studies reviewed here further support this view. Therefore, the anxiolytic efficacy of cyamemazine in benzodiazepine withdrawal can be due to a 5-HT(2AR) antagonistic activity at the cortical level.
authors.affiliation: Inserm U669, University Hospital Paul Brousse, Villejuif, France. amine.benyamina@pbr.aphp.fr
authors.forename: Amine
authors.initials: A
authors.lastname: Benyamina
authors.forename: Mickaël
authors.initials: M
authors.lastname: Naassila
authors.forename: Michel
authors.initials: M
authors.lastname: Bourin
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects*; D006801:Humans; D010640:Phenothiazines / Q000494:pharmacology* / Q000627:therapeutic use; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
chemical_list: D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D010640:Phenothiazines; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D001569:Benzodiazepines; C028457:cyamemazine