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- W2087307508 abstract "All antipsychtics currently in clinical use are antagonists or weak partial agonists at the dopamine D2 receptor (D2R). Antipsychotic medication is associated with adverse effects such as extrapyramidal symptoms (EPS). The lower EPS liability of newer, so-called atypical antipsychotics, typified by clozapine, has been proposed to reflect their faster rates of dissociation from the D2R, as compared to older, typical antipsychotics such as haloperidol. This hypothesis has received increasing attention in recent years, and several pharmaceutical companies have endeavored to developed their own fast off-antipsychotics. However, previous studies have measured dissociation of radiolabeled antipsychotics or used modified G proteins to study receptor activation-induced calcium release, which confers certain limitations in terms of temporal resolution. We have examined antagonist dissociation in living cells, employing an assay based on the activation of G protein coupled potassium channels. This assay uses native G proteins and has higher temporal resolution than previous studies. Our preliminary data suggest that there may be larger differences between different atypical antipsychotics than has previously been appreciated. Furthermore, the differences between atypical and typical drugs appear to relate mainly to the differential hydrophilicities of these drugs." @default.
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- W2087307508 date "2013-01-01" @default.
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- W2087307508 title "Novel Aspects of the Reversibility of the Antagonism at the Dopamine D2 Receptor by Antipsychotics" @default.
- W2087307508 doi "https://doi.org/10.1016/j.bpj.2012.11.183" @default.
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