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Titolo:
A NOVEL MUSCARINIC RECEPTOR-LIGAND WHICH PENETRATES THE BLOOD-BRAIN-BARRIER AND DISPLAYS IN-VIVO SELECTIVITY FOR THE M2 SUBTYPE
Autore:
GITLER MS; COHEN VI; DELACRUZ R; BOULAY SF; JIN BY; ZEEBERG BR; REBA RC;
Indirizzi:
GEORGE WASHINGTON UNIV,MED CTR,DEPT RADIOL,RADIOPHARMACEUT CHEM SECT,ROOM 662 ROSS HALL WASHINGTON DC 20037 GEORGE WASHINGTON UNIV,MED CTR,DEPT RADIOL,RADIOPHARMACEUT CHEM SECT,ROOM 662 ROSS HALL WASHINGTON DC 20037 UNIV CHICAGO HOSP & CLIN,DEPT CLIN GENET,NUCL MED SECT CHICAGO IL 60637
Titolo Testata:
Life sciences
fascicolo: 23, volume: 53, anno: 1993,
pagine: 1743 - 1751
SICI:
0024-3205(1993)53:23<1743:ANMRWP>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
AF-DX 116; RAT-BRAIN; POTENTIAL RADIOPHARMACEUTICALS; AUTORADIOGRAPHIC DISTRIBUTION; ACETYLCHOLINE-RECEPTORS; ALZHEIMERS-DISEASE; BINDING; TOMOGRAPHY; SPECT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
27
Recensione:
Indirizzi per estratti:
Citazione:
M.S. Gitler et al., "A NOVEL MUSCARINIC RECEPTOR-LIGAND WHICH PENETRATES THE BLOOD-BRAIN-BARRIER AND DISPLAYS IN-VIVO SELECTIVITY FOR THE M2 SUBTYPE", Life sciences, 53(23), 1993, pp. 1743-1751

Abstract

Alzheimer's disease (AD) involves selective loss of muscarinic m2, but not ml, subtype neuroreceptors in the posterior parietal cortex of the human brain. Emission tomographic study of the loss of m2 receptorsin AD is limited by the fact that there is currently no available m2-selective radioligand which can penetrate the blood-brain barrier. In our efforts to prepare such a radioligand, we have used competition studies against currently existing muscarinic receptor radioligands to infer the in vitro and in vivo properties of a novel muscarinic receptor ligand, o)butyl]-1-phenyl]acetyl]-10,11-dihydro-5H-dibenzo [b,e][1,4]diazepin-11-one (DIBD). In vitro competition studies against [H-3](R)-3-quinuclidinylbenzilate ([H-3]QNB) and [H-3]N-methylscopolamine ([H-3]NMS), using membranes derived from transfected cells expressing onlyml, m2, m3, or m4 receptor subtypes, indicate that DIBD is selective for m2/m4 over ml/m3. In vivo competition studies against (R,R)-[I-125]IQNB indicate that DIBD crosses the blood brain barrier (BBB). The relationship of the regional percentage decrease in (R,R)-[I-125]IQNB versus the percentage of each of the receptor subtypes indicates that DIBD competes more effectively in those brain regions which are known tobe enriched in the m2, relative to the ml, m3, and m4, receptor subtype; however, analysis of the data using a mathematical model shows that caution is required when interpreting the in vivo results. We conclude that a suitably radiolabeled derivative of DIBD may be of potentialuse in emission tomographic study of changes in m2 receptors in the central nervous system.

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Documento generato il 30/11/20 alle ore 19:46:14