Aim: Deterioration of cognition, worsening of frailty, and pneumonia may be exacerbated by long-term treatment with medications having anticholinergic activity. The potency of anticholinergic activity in antipsychotics is reported in the literature, but potency or the order of potency was not found to coincide with each other. Therefore, we evaluated anticholinergic activity in antipsychotics by radio-receptor assay using a M1WT3 cell line expressing muscarinic-1 receptor.
Methods: We established an eco-friendly method of changing the scintillator in a radio-receptor assay system from liquid to solid using a M1WT3 cell membrane. With this method, we evaluated the anticholinergic activity of chlorpromazine, clozapine, perphenazine, pimozide, fluphenazine, and olanzapine, which show differences in anticholinergic potency as per the available literature, and aripiprazole and risperidone, which are frequently prescribed in psychiatry nowadays. To evaluate the potential appearance of anticholinergic side effects, anticholinergic activity in this report and the serum concentration range reported in a manufacturer's interview form were compared. We created a classification model of the potential appearance of anticholinergic side effects with reference to a report by Salahudeen et al. and later added one report each by Ohara et al., Nagai et al., and Huhn et al.
Results: The IC50 (50% inhibition of quinuclidinyl benzylate binding) value of clozapine was the most potent among the evaluated compounds at 0.028±0.007 μM, followed by chlorpromazine 0.149±0.001 μM > olanzapine 0.382±0.195 μM > perphenazine 6.78±1.31 μM > pimozide 7.25±3.51 μM > fluphenazine 8.95±3.15 μM > risperidone 10.638±7.054 μM > aripiprazole 28.44±4.52 μM. Our results are very close to those reported by Huhn et al., which involved 50,000 patients prescribed with antipsychotics possessing anticholinergic activity.
Discussion: Among the evaluated antipsychotics, aripiprazole showed the lowest anticholinergic activity and is possibly free of side effects causing cognitive worsening. The radio-receptor binding assay we developed using the M1WT3 cell line can potentially be useful in monitoring side effects of deterioration of cognition in patients treated with antipsychotics.
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