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7916490

Source:http://linkedlifedata.com/resource/pubmed/id/7916490

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pubmed-article:7916490pubmed:abstractTextAlmost no information is available concerning the link between clinical effects of dopamine D2 receptor agonists in the treatment of Parkinson's disease (PD) and the extent of D2 receptor occupancy in the brain. Therefore, we investigated the possible correlation between administration of behaviorally active doses of the selective D2 agonist LY 171555 and in vivo D2 receptor occupancy in the unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-lesioned rhesus monkey model of PD. Single photon emission computed tomography (SPECT) with the D2 receptor antagonist [123I]IBZM (iodobenzamide) as radioligand was used to estimate the receptor occupancy. The MPTP-lesioned monkeys consistently showed signs of unilateral parkinsonism. LY 171555 (0.01 or 0.3 mg/kg) significantly increased contralateral rotation (away from the lesion), being most effective at the lower dose. In the MPTP-lesioned monkeys [123I]IBZM activity in the left (lesioned) striatum was significantly higher as compared to that in the right striatum. Only upon administration of 0.3 mg/kg LY 171555 a significant amount of receptor occupancy by LY 171555, as measured with [123I]IBZM SPECT, at both lesioned and non-lesioned side, was detected. Using D2 receptor mediated inhibition of the evoked release of [3H]acetylcholine from rat striatal tissue as a functional model, we showed that the lack of effect with 0.01 mg/kg LY 171555 was not due to non-competitive interaction between LY 171555 and IBZM at the D2 receptor. We conclude that the D2 antagonist [123I]IBZM is not a suitable SPECT ligand to study the relationship between behavioral effects of the selective D2 agonist LY 171555 in unilaterally MPTP-lesioned monkeys and the D2 receptor occupancy in vivo in this animal model of PD.lld:pubmed
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pubmed-article:7916490pubmed:articleTitleNo direct correlation between behaviorally active doses of the dopamine D2 agonist LY 171555 and displacement of [123I]IBZM as measured with SPECT in MPTP monkeys.lld:pubmed
pubmed-article:7916490pubmed:affiliationDepartment of Neurology, Graduate School Neuroscience Amsterdam, Vrije Universiteit, Rijswijk, The Netherlands.lld:pubmed
pubmed-article:7916490pubmed:publicationTypeJournal Articlelld:pubmed
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