000001695 001__ 1695 000001695 005__ 20180208225327.0 000001695 0247_ $$2pmid$$apmid:19545560 000001695 0247_ $$2DOI$$a10.1016/j.ejphar.2009.06.025 000001695 0247_ $$2WOS$$aWOS:000269933100017 000001695 037__ $$aPreJuSER-1695 000001695 041__ $$aeng 000001695 082__ $$a610 000001695 084__ $$2WoS$$aPharmacology & Pharmacy 000001695 1001_ $$0P:(DE-Juel1)VDB17596$$aSihver, W.$$b0$$uFZJ 000001695 245__ $$aAutoradiographic comparison of in vitro binding characteristics of various tritiated adenosine A2A receptor ligands in rat, mouse and pig brain and first ex vivo results 000001695 260__ $$aAmsterdam$$bElsevier$$c2009 000001695 300__ $$a 000001695 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article 000001695 3367_ $$2DataCite$$aOutput Types/Journal article 000001695 3367_ $$00$$2EndNote$$aJournal Article 000001695 3367_ $$2BibTeX$$aARTICLE 000001695 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000001695 3367_ $$2DRIVER$$aarticle 000001695 440_0 $$021162$$aEuropean Journal of Pharmacology$$v616$$x0926-6917$$y1 000001695 500__ $$aRecord converted from VDB: 12.11.2012 000001695 520__ $$aThe adenosine A(2A) receptor in the basal ganglia is involved in the control of movement and plays a role in movement disorders such as Parkinsonism. Developing ligands to evaluate that receptor by noninvasive methods such as positron emission tomography has a high priority. In vitro radioligand binding guides the selection of ligands for in vivo application. This study measured the binding of the adenosine A(2A) receptor antagonist [(3)H]MSX-2 (3-(3-hydroxypropyl)-8-m-methoxystyryl)-7-methyl-1-propargylxanthine) to rat, mouse and pig brain by autoradiography. Other studies measured binding to membranes from PC12 pheochromocytoma cells. Those binding parameters were compared to those of the adenosine A(2A) receptor antagonist [(3)H]ZM241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino)ethyl)phenol), the adenosine A(2A) receptor agonist [(3)H]CGS21680 (2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamidoadenosine) and the unselective adenosine receptor agonist [(3)H]NECA (5'N-ethylcarboxamido)adenosine). The potency order (K(d)) in the three species was [(3)H]ZM241385<[(3)H]MSX-2<[(3)H]NECA<[(3)H]CGS21680. The density of [(3)H]MSX-2 binding sites was greater in the striatum than in the cortex. Preliminary ex vivo experiments showed that by 10min after iv injection, [(3)H]MSX-2 and [(3)H]CGS21680 crossed the blood-brain barrier to the extent of almost 1% ID/g brain tissue, but [(3)H]NECA and [(3)H]ZM241385 to only 0.2% ID/g. The prior administration of unlabeled ZM241385 significantly lowered brain uptake of [(3)H]MSX-2. In conclusion, [(3)H]MSX-2 has a high affinity and sufficient selectivity for the adenosine A(2A) receptor. It penetrates the blood-brain barrier. Sensitivity to photoisomerization is a limitation. Further investigations assess its suitability as a ligand for imaging the brain adenosine A(2A) receptor. 000001695 536__ $$0G:(DE-Juel1)FUEK409$$2G:(DE-HGF)$$aFunktion und Dysfunktion des Nervensystems$$cP33$$x0 000001695 588__ $$aDataset connected to Web of Science, Pubmed 000001695 650_2 $$2MeSH$$aAdenosine A2 Receptor Agonists 000001695 650_2 $$2MeSH$$aAnimals 000001695 650_2 $$2MeSH$$aAutoradiography 000001695 650_2 $$2MeSH$$aBlood-Brain Barrier: metabolism 000001695 650_2 $$2MeSH$$aBrain: metabolism 000001695 650_2 $$2MeSH$$aCell Membrane: metabolism 000001695 650_2 $$2MeSH$$aChromatography, High Pressure Liquid 000001695 650_2 $$2MeSH$$aFemale 000001695 650_2 $$2MeSH$$aLigands 000001695 650_2 $$2MeSH$$aMice 000001695 650_2 $$2MeSH$$aPC12 Cells 000001695 650_2 $$2MeSH$$aProtein Binding 000001695 650_2 $$2MeSH$$aRats 000001695 650_2 $$2MeSH$$aReceptor, Adenosine A2A: metabolism 000001695 650_2 $$2MeSH$$aSwine 000001695 650_2 $$2MeSH$$aTritium: chemistry 000001695 650_2 $$2MeSH$$aXanthines: chemistry 000001695 650_2 $$2MeSH$$aXanthines: metabolism 000001695 650_7 $$00$$2NLM Chemicals$$aAdenosine A2 Receptor Agonists 000001695 650_7 $$00$$2NLM Chemicals$$aLigands 000001695 650_7 $$00$$2NLM Chemicals$$aMSX 2 compound 000001695 650_7 $$00$$2NLM Chemicals$$aReceptor, Adenosine A2A 000001695 650_7 $$00$$2NLM Chemicals$$aXanthines 000001695 650_7 $$010028-17-8$$2NLM Chemicals$$aTritium 000001695 650_7 $$2WoSType$$aJ 000001695 65320 $$2Author$$aAdenosine A(2A) receptor 000001695 65320 $$2Author$$a[H-3]ZM241385 000001695 65320 $$2Author$$a[H-3]CGS21680 000001695 65320 $$2Author$$a[H-3]MSX-2 000001695 65320 $$2Author$$a[H-3]NECA 000001695 65320 $$2Author$$aBrain imaging 000001695 7001_ $$0P:(DE-Juel1)VDB17597$$aSchulze, A.$$b1$$uFZJ 000001695 7001_ $$0P:(DE-Juel1)VDB12398$$aWutz, W.$$b2$$uFZJ 000001695 7001_ $$0P:(DE-Juel1)VDB59407$$aStüsgen, S.$$b3$$uFZJ 000001695 7001_ $$0P:(DE-HGF)0$$aOlsson, R. 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