Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 140, Issue 2, Pages 197-200Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2019.05.006
Keywords
Antipsychotics; Anticholinergic effect; Mouse cerebral cortex
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Funding
- Joint Research Grants of the Toho University Faculty of Pharmaceutical Sciences
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Antipsychotics are often the first-line treatment for behavioral and psychological symptoms of dementia. However, the potential anticholinergic effects of antipsychotics could counteract the therapeutic effects of cholinesterase inhibitors used to treat dementia. We investigated the inhibitory effects of 26 antipsychotics on [N-Methyl-H-3] scopolamine specific binding in mouse cerebral cortex. At 10(-5) M, chlorpromazine, levomepromazine, prochlorperazine, timiperone, zotepine, pimozide, blonanserin, olanzapine, quetiapine, and clozapine inhibited [N-Methyl-H-3] scopolamine binding by >45%. Furthermore, the pK(i) values of chlorpromazine, levomepromazine, zotepine, olanzapine, and clozapine overlapped with their clinically achievable blood concentrations. Therefore, the anticholinergic properties of these antipsychotics could attenuate the effects of cholinesterase inhibitors. (C) 2019 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.
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