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Titolo:
Binding characteristics of selective serotonin reuptake inhibitors with relation to emission tomography studies
Autore:
Elfving, B; Bjornholm, B; Ebert, B; Knudsen, GM;
Indirizzi:
Univ Copenhagen Hosp, Rigshosp, Neurobiol Res Unit N9201, DK-2100 Copenhagen, Denmark Univ Copenhagen Hosp Copenhagen Denmark DK-2100 2100 Copenhagen, Denmark H Lundbeck AS, Dept Computat Chem, DK-2500 Copenhagen, Denmark H Lundbeck AS Copenhagen Denmark DK-2500 em, DK-2500 Copenhagen, Denmark Royal Danish Sch Pharm, Dept Pharmacol, DK-2100 Copenhagen, Denmark Royal Danish Sch Pharm Copenhagen Denmark DK-2100 00 Copenhagen, Denmark
Titolo Testata:
SYNAPSE
fascicolo: 3, volume: 41, anno: 2001,
pagine: 203 - 211
SICI:
0887-4476(200109)41:3<203:BCOSSR>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
H-3 CITALOPRAM BINDING; UPTAKE SITES; HUMAN-BRAIN; RAT-BRAIN; IN-VITRO; 5-HYDROXYTRYPTAMINE TRANSPORTER; TEMPERATURE-DEPENDENCE; COMPUTED-TOMOGRAPHY; PLATELET MEMBRANES; C-11 (+)MCN5652;
Keywords:
[H-3]-(+)-McN5652; [H-3]-(S)-citalopram; SSRI; rat brain; temperature; logP; receptor binding;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Elfving, B Univ Copenhagen Hosp, Rigshosp, Neurobiol Res Unit N9201, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark Univ Copenhagen Hosp 9 Blegdamsvej Copenhagen Denmark DK-2100
Citazione:
B. Elfving et al., "Binding characteristics of selective serotonin reuptake inhibitors with relation to emission tomography studies", SYNAPSE, 41(3), 2001, pp. 203-211

Abstract

When developing ligands for emission tomography studies, one of the major obstacles lies in the selection of ligand candidates. A previously unattended factor such as the influence of temperature on candidate ligand affinityis likely to play a role. By use of rat brain homogenates, the binding characteristics of [H-3]-(S)-citalopram and [H-3]-(+)-McN5652 and the receptor-ligand interaction at the serotonin transporter of 17 selective serotonin reuptake inhibitors were compared at 21 degreesC and 37 degreesC, respectively. Ligand logP values were also calculated. The ratios for K-i at 37 degreesC vs. 21 degreesC varied between 0.2 and 2.2 for the selective serotoninreuptake inhibitors considered in this study, with most of the ligands displaying an inverse relationship between K-i and temperature. Ten of the 17 selective serotonin reuptake inhibitors were found to have pK(i) values statistically significantly different at 21 degreesC compared to 37 degreesC (P < 0.05). The logP values ranged between 3.6 and 4.8, except for DASB, 5-iodo-6-nitroquipazine, and paroxetine where logP was 1.9, 2.2, and 5.0, respectively. K-d was 0.71 nM at 37<degrees>C and 0.31 nM at 21 degreesC for [H-3]-(S)-citalopram. For [H-3]-(+)-McN5652 K-d was 0.11 nM at 37 degreesC and 0.08 nM at 21 degreesC. The association and dissociation was much faster for [H-3]-(S)-citalopram as compared to [H-3]-(+)-McN5652. It is concluded that temperature may affect K-d differently and that in vitro dissociation may help to predict whether a given ligand may be useful in PET studies. LogP values do not per se predict the potential of a given ligand as an emission tomography tracer. Synapse 41: 203-211,2001. (C) 2001 Wiley-Liss, Inc.

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Documento generato il 27/01/20 alle ore 07:20:52