Disease relevance of Kyamepromazine

• PATIENT: A woman who developed three episodes of drug-induced hepatitis within 3 years as a result of successive treatment with two tricyclic antidepressants, trimipramine and desipramine, and one neuroleptic derivative, cyamemazine [1].

Psychiatry related information on Kyamepromazine

• We suggest that cyamemazine could reduce alcohol consumption by antagonizing the activation of the dopaminergic pathways during the induction of alcohol dependence [2].
• These 5-HT3- and 5-HT2C-antagonistic actions of cyamemazine can be involved, at least in part, in its beneficial therapeutic actions in anxiety disorders [3].
• Acute or chronic administration of cyamemazine dramatically decreases the spontaneous locomotor activity of mice at the dose of 1 mg/kg in comparison with the control group [4].
• CONCLUSIONS: Cyamemazine showed similar efficacy and tolerability to diazepam for the treatment of alcohol withdrawal symptoms at therapeutic doses in the range 100-300 mg [5].

High impact information on Kyamepromazine

• A positron emission tomography (PET) study of cerebral dopamine D2 and serotonine 5-HT2A receptor occupancy in patients treated with cyamemazine (Tercian) [6].
• In addition, cyamemazine was tested in other brain receptor types and subtypes which are considered to mediate central nervous systems effects of drugs [7].
• Finally, in rat brain membranes cyamemazine antagonized 5-HT2C-dependent PLC stimulation with Ki = 424 nM (mianserin exhibits a Ki = 113 nM) [3].
• OBJECTIVE: The present study was undertaken to establish whether cyamemazine antagonizes 5-HT3- and/or 5-HT2C-mediated responses, and whether it compares with reference compounds [3].
• The action of cyamemazine on 5-HT3 receptors could also explain its effect on alcohol convulsions during withdrawal convulsions [2].

Chemical compound and disease context of Kyamepromazine

• RESULTS: After three episodes of drug-induced hepatitis the patient's serum aspartate aminotransferase and alanine aminotransferase levels returned to normal when the tricyclic antidepressants and cyamemazine were withdrawn [1].

Biological context of Kyamepromazine

• The lowest dose of cyamemazine had no effect on alcohol intake but increased food intake [2].
• Cyamemazine reduced hERG current amplitude with an IC50 value of 470 nM [8].
• Tissue distribution of cyamemazine is discussed in light of the existing literature [9].
• Preclinical and clinical pharmacology of cyamemazine: anxiolytic effects and prevention of alcohol and benzodiazepine withdrawal syndrome [10].
• Lipid peroxidation and cell death have been chosen as model photobiological damage induced by UVA alone or photosensitized by cyamemazine (CMZ) and its photoproduct possessing phototoxic properties [11].

Anatomical context of Kyamepromazine

• METHODS: Cyamemazine was tested for its ability to antagonize: (i) 5-HT3-dependent contraction of the isolated guinea-pig ileum and bradycardic responses in the rat and (ii) 5-HT2C-dependent phospholipase C (PLC) stimulation in rat brain membranes [3].
• In isolated guinea pig trachea, cyamemazine reduced maximum contractile responses to serotonin with pIC(50)=7.92+/-0.35, (n=4), whereas ketanserin exhibited a pIC(50)=8.79 [12].
• An insight into the mechanisms of the phototoxic response induced by cyamemazine in cultured fibroblasts and keratinocytes [13].
• 5-HT2A receptor antagonist properties of cyamemazine in rat and guinea pig smooth muscle [12].
• Contrasting action of flavonoids on phototoxic effects induced in human skin fibroblasts by UVA alone or UVA plus cyamemazine, a phototoxic neuroleptic [11].

Associations of Kyamepromazine with other chemical compounds

• Recently, an in vitro study showed that cyamemazine possesses high affinity for serotonin 5-HT(2A) receptors, which was fourfold higher than its affinity for dopamine D(2) receptors (Hameg et al. 2003) [6].
• The effect of cyamemazine a dopamine D2 receptor antagonist on voluntary ethanol consumption in rats and on ethanol withdrawal in mice was examined [2].
• METHOD: A multicenter, randomized, double-blind study in 89 alcohol-dependent patients (CIWA-Ar score between 10 and 30), electing an alcohol withdrawal procedure, was used to find effective doses of cyamemazine and to compare it with diazepam for efficacy and tolerability [5].

Gene context of Kyamepromazine

• Effects of cyamemazine on hERG, INa, ICa, Ito, Isus and IK1 channel currents, and on the QTc interval in guinea pigs [8].

Analytical, diagnostic and therapeutic context of Kyamepromazine

• 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 [6].
• Rats prepared for microdialysis (striatum) were intraperitoneally given cyamemazine 1 mg/kg, 5 mg/kg or vehicle ( n=4 in each group) [14].
• Cyamemazine was formally identified in postmortem blood using an HPLC-DAD screening procedure, and then quantified in some postmortem samples by means of a specific HPLC method [9].

References