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• W2124981036 abstract "The excellent article by Clark-Papasavas et al. (2014) reported that amisulpiride improved delusions hallucinations and agitation in four patients with Alzheimer's disease at the low dose of 25–50 mg/day. They also found that this dose range occupied 47–70% of the dopamine D2 receptors in the caudate and 31–58% in the putamen when measured by means of [18F]fallypride positron emission tomography. The purpose of this present comment is to indicate that the D2 occupancies may actually be higher when measured by [11C]raclopride. This is because [18F]fallypride is tightly bound to the D2 receptor with a low dissociation constant of 0.03 nM (similar to the value of 0.02–0.06 nM for spiperone), whereas [11C]raclopride is relatively loosely attached to the D2 receptor with a higher dissociation constant of 1.9 nM (Seeman and Van Tol, 1995; Seeman, 2011). The tight attachment of [18F]fallypride to the D2 receptor increases the concentration of an antipsychotic needed to compete with [18F]fallypride, as compared with [11C]raclopride. In fact, in a series of 21 antipsychotic drugs, the concentration of each antipsychotic needed to compete with [3H]spiperone is three times higher than that needed to compete with [3H]raclopride (Seeman, 2011). Considering that [18F]fallypride is tightly bound to D2, therefore, the amisulpride occupancies of D2 reported by Clark-Papasavas et al. would actually be higher when measured by [11C]raclopride. Such higher values of D2 occupation by amisulpride would bring the amisulpride occupancies of D2 into the usual antipsychotic range of 60–80% occupancy, as established by Farde's group for the treatment of psychosis in schizophrenia (Nyberg et al., 1996), and in agreement with the values of 60–80% occupation of D2 by amisulpride in treating schizophrenia as measured by [123I]IBZM (la Fougère et al., 2005). Although the different radio-ligands involve different methodological details, the final occupancies of the D2 receptors are generally comparable. The antipsychotic doses of 25–50 mg amisulpride that were found effective by Clark-Papasavas et al. in treating the delusions, hallucinations, and aggression in patients with Alzheimer's disease were unusually low, as compared with the customary dose range of 400–800 mg/day for amisulpride in treating psychotic symptoms in schizophrenia. It is possible that the permeation of amisulpride into the brain may be increased in Alzheimer's disease, either as a result of a reduction in the drug-exporting P-glycoprotein or an increased general permeability of the blood/brain barrier. None declared." @default.
• W2124981036 created "2016-06-24" @default.
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• W2124981036 date "2014-09-25" @default.
• W2124981036 modified "2023-10-09" @default.
• W2124981036 title "Therapeutic occupation of dopamine D2 antipsychotic receptors in Alzheimer's disease" @default.
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• W2124981036 doi "https://doi.org/10.1002/gps.4133" @default.
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