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Titolo:
Z-IQNP: a potential radioligand for SPECT imaging of muscarinic acetylcholine receptors in Alzheimer's disease
Autore:
Nobuhara, K; Halldin, C; Hall, H; Karlsson, P; Farde, L; Hiltunen, J; McPherson, DW; Savonen, A; Bergstrom, KA; Pauli, S; Swahn, CG; Larsson, SA; Schnell, PO; Sedvall, G;
Indirizzi:
Karolinska Inst, Karolinska Hosp, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden Karolinska Inst Stockholm Sweden S-17176 Sect, S-17176 Stockholm, Sweden Karolinska Inst, Karolinska Hosp, Dept Radiat Phys, S-17176 Stockholm, Sweden Karolinska Inst Stockholm Sweden S-17176 Phys, S-17176 Stockholm, Sweden MAP Med Technol Oy, Tikkakoski 41160, Finland MAP Med Technol Oy Tikkakoski Finland 41160 y, Tikkakoski 41160, Finland Oak Ridge Natl Lab, Nucl Med Grp, Div Life Sci, Oak Ridge, TN 37831 USA Oak Ridge Natl Lab Oak Ridge TN USA 37831 fe Sci, Oak Ridge, TN 37831 USA Kuopio Univ Hosp, Dept Clin Physiol, SF-70210 Kuopio, Finland Kuopio Univ Hosp Kuopio Finland SF-70210 ysiol, SF-70210 Kuopio, Finland
Titolo Testata:
PSYCHOPHARMACOLOGY
fascicolo: 1, volume: 149, anno: 2000,
pagine: 45 - 55
Fonte:
ISI
Lingua:
ENG
Soggetto:
IODINE-125-LABELED 1-AZABICYCLO<2.2.2>OCT-3-YL ALPHA-HYDROXY-ALPHA-(1-IODO-1-PRO; POSITRON EMISSION TOMOGRAPHY; POSTMORTEM HUMAN-BRAIN; GUINEA-PIG BRAIN; RAT-BRAIN; BINDING-SITES; CHOLINERGIC RECEPTORS; COMPUTED-TOMOGRAPHY; CEREBRAL-CORTEX; SIGMA-RECEPTOR;
Keywords:
Z-IQNP; SPECT; autoradiography; Alzheimer's disease; muscarinic acetylcholine receptor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Nobuhara, K Karolinska Inst, Karolinska Hosp, Dept Clin Neurosci, PsychiatSect, S-17176 Stockholm, Sweden Karolinska Inst Stockholm Sweden S-171766 Stockholm, Sweden
Citazione:
K. Nobuhara et al., "Z-IQNP: a potential radioligand for SPECT imaging of muscarinic acetylcholine receptors in Alzheimer's disease", PSYCHOPHAR, 149(1), 2000, pp. 45-55

Abstract

Rationale: The density of the M2 subtype of muscarinic acetylcholine receptors (mAChR) has been shown to be reduced in the brain of patients with Alzheimer's disease (AD). It is therefore of interest to develop a brain imaging method for diagnostic purposes. Z-(R,R)-1-azabicyclo[2.2.2] oct-3-yl alpha-hydroxy-alpha-(1-iodol-propen-3-yl)-alpha-phenylacetate (Z-IQNP) is a muscarinic antagonist with high affinity for the M2 subtype. Objective. The pharmacological characteristics and topographic distribution of radiolabelled Z-IQNP as a radioligand for the M2 mAChR subtype were examined in vitro and in vivo. Methods: Z-IQNP was labelled with I-125 and I-123. Autoradiography was performed on whole-hemisphere cryosections from human post mortem brains. SPECT was performed in a cynomolgus monkey. Results: Autoradiographyshowed binding of [I-125]Z-IQNP in all brain regions, which was inhibited by the non-selective muscarinic antagonist scopolamine. The addition of BIBN 99, a compound with high affinity for the M2 subtype, inhibited [I-125]Z-IQNP binding particularly in the cerebellum, which has a high density of the M2 subtype. SPECT demonstrated high uptake of [I-123]Z-IQNP in all brain regions. The binding was markedly reduced in all brain regions after pretreatment with the non-selective muscarinic antagonist dexetimide and also theM1 antagonist biperiden. Dexetimide markedly inhibited [I-123]Z-IQNP binding in the cerebellum, which is consistent with a high density of M2-receptors in this region. The sigma receptor binding compound DuP 734 had no effect on Z-IQNP binding either in vitro or in vivo. Conclusions: This study indicates that radiolabelled Z-IQNP has high specificity for mAChR with higheraffinity for the M-2 than the M-1 subtype and negligible affinity for sigma recognition sites both in vitro and in vivo. [I-123]Z-IQNP should be useful for future SPECT studies in AD for examination of the density of M2 receptors particularly in the cerebellum.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 07:38:14