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Binding characteristics of selective serotonin reuptake inhibitors with relation to emission tomography studies
Author(s) -
Elfving Betina,
Bjørnholm Berith,
Ebert Bjarke,
Knudsen Gitte Moos
Publication year - 2001
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.1076
Subject(s) - citalopram , serotonin transporter , chemistry , reuptake inhibitor , serotonin reuptake inhibitor , serotonin , ligand (biochemistry) , paroxetine , reuptake , serotonin plasma membrane transport proteins , serotonin uptake inhibitors , pharmacology , medicine , receptor , biochemistry , fluoxetine
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 affinity is likely to play a role. By use of rat brain homogenates, the binding characteristics of [ 3 H]‐(S)‐citalopram and [ 3 H]‐(+)‐McN5652 and the receptor‐ligand interaction at the serotonin transporter of 17 selective serotonin reuptake inhibitors were compared at 21°C and 37°C, respectively. Ligand logP values were also calculated. The ratios for K i at 37°C vs. 21°C varied between 0.2 and 2.2 for the selective serotonin reuptake 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°C compared to 37°C ( 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°C and 0.31 nM at 21°C for [ 3 H]‐(S)‐citalopram. For [ 3 H]‐(+)‐McN5652 K d was 0.11 nM at 37°C and 0.08 nM at 21°C. The association and dissociation was much faster for [ 3 H]‐(S)‐citalopram as compared to [ 3 H]‐(+)‐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. © 2001 Wiley‐Liss, Inc.