Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
RESOLUTION AND IN-VITRO AND INITIAL IN-VIVO EVALUATION OF ISOMERS OF IODINE-125-LABELED 1-AZABICYCLO[2.2.2]OCT-3-YL Y-ALPHA-(1-IODO-1-PROPEN-3-YL)-ALPHA-PHENYLACETATE - A HIGH-AFFINITY LIGAND FOR THE MUSCARINIC RECEPTOR
Autore:
MCPHERSON DW; LAMBERT CR; JAHN K; SOOD V; MCREE RC; ZEEBERG B; REBA RC; KNAPP FFR;
Indirizzi:
OAK RIDGE NATL LAB,DIV HLTH SCI RES,NUCL MED GRP,BLDG 4501,MAIL STOP 6229POB 2008 OAK RIDGE TN 37831 GEORGE WASHINGTON UNIV,MED CTR,DIV NUCL MED,RADIOPHARMACEUT CHEM SECTWASHINGTON DC 20037 UNIV CHICAGO,DEPT RADIOL,NUCL MED SECT CHICAGO IL 60637
Titolo Testata:
Journal of medicinal chemistry
fascicolo: 20, volume: 38, anno: 1995,
pagine: 3908 - 3917
SICI:
0022-2623(1995)38:20<3908:RAIAII>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
EMISSION COMPUTED-TOMOGRAPHY; ACETYLCHOLINE-RECEPTORS; 3-QUINUCLIDINYL BENZILATE; ALZHEIMERS-DISEASE; POTENTIAL RADIOPHARMACEUTICALS; CHOLINERGIC RECEPTOR; OPTICAL ISOMERS; HUMAN-BRAIN; RAT-BRAIN; BINDING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
D.W. Mcpherson et al., "RESOLUTION AND IN-VITRO AND INITIAL IN-VIVO EVALUATION OF ISOMERS OF IODINE-125-LABELED 1-AZABICYCLO[2.2.2]OCT-3-YL Y-ALPHA-(1-IODO-1-PROPEN-3-YL)-ALPHA-PHENYLACETATE - A HIGH-AFFINITY LIGAND FOR THE MUSCARINIC RECEPTOR", Journal of medicinal chemistry, 38(20), 1995, pp. 3908-3917

Abstract

1-Azabicyclo[2.2.2]oct-3-yl y-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (IQNP, 1), is a highly selective ligand for the muscarinic acetylcholinergic receptor (mAChR). There are eight stereoisomers in the racemic mixture. The optical isomers of a-hydroxy-alpha-phenyl-alpha-(1-propyn-3-yl)acetic acid were resolved as the alpha-methylbenzylamine salts, and the optical isomers of 3-quinuclidinol were resolved as the tartrate salts. The E and Z isomers were prepared by varying the reaction conditions for the stannylation of the triple bond followed bypurification utilizing flash column chromatography. In vitro binding assay of the four stereoisomers containing the (R)-(-)-3-quinuclidinylester demonstrated that each isomer of 1 bound to mAChR with high affinity. In addition, (E)-(-)-(-)-IQNP demonstrated the highest receptorsubtype specificity between the ml molecular subtype (K-D, nM, 0.383 /- 0.102) and the m2 molecular subtype (29.6 +/- 9.70). In vivo biodistribution studies demonstrated that iodine-125-labeled (E)-(-)-(+)-1 cleared rapidly from the brain and heart. In contrast, iodine-125-labeled (E)-(-)-(-)-, (Z)-(-)-(-)-, and (Z)-(-)-(+)-1 have high uptake andretention in mAChR rich areas of the brain. It was also observed that(E)-(-)-(-)-IQNP demonstrated an apparent subtype selectivity in vivo with retention in M(1) (m1, m4) mAChR areas of the rain. In addition, (Z)-(-)-(-)-IQNP also demonstrated significant uptake in tissues containing the M(2) (m2) mAChR subtype. These results demonstrate that the iodine-123-labeled analogues of the (E)-(-)-(-)- and (Z)-(-)-(-)-IQNP isomers are attractive candidates for single-photon emission-computed tomographic imaging of cerebral and cardiac mAChR receptor densities.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/11/20 alle ore 21:42:12