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Binding of [ 123 I]beta‐CIT to brain serotonin and dopamine transporters (SERT & DAT) after multiple dose administration of sertraline
Author(s) -
Gibbs M. A.,
Rogers J. F.,
Marek G. J.,
Stiger T. R.,
Marek K. L.,
Seibyl J. P.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.077
Subject(s) - sertraline , binding potential , reuptake inhibitor , citalopram , pharmacology , placebo , serotonin , serotonin reuptake inhibitor , medicine , psychology , dopamine , endocrinology , antidepressant , receptor , alternative medicine , pathology , hippocampus
Previous work suggests that virtual saturation of brain SERT occurs after administration of therapeutic doses of selective serotonin reuptake inhibitors (SSRIs). This study determined [ 123 I]β‐CIT binding in the brain after multiple dose (8 days) administration of sertraline 25mg and 50mg (randomized, double‐blinded, placebo controlled) and 150mg (open‐label, preceded by 50mg QD × 3 days and 100mg QD × 3 days) with a 7–day washout after the first 2 periods. Six healthy subjects had baseline brain single photon emission computed tomography scans with [ 123 I]β‐CIT, a high affinity SERT and DAT radiotracer. Follow‐up scans occurred 1h after the day 8 sertraline dose for each period (20‐24h after [ 123 I]β‐CIT infusion). Mean±SD [ 123 I]β‐CIT binding in the brainstem (baseline 1.65±0.39, follow‐up 0.77±0.3) and the striatum (baseline 9.79±3.48, follow‐up 8.17±2.66) was used to estimate percent displacement by sertraline 150mg at SERT (53%) and DAT (17%), respectively. Results from the double‐blind portion of the study are pending. Brainstem displacement was comparable to historical citalopram (40mg/day) data (51%) and appears to represent SERT saturation. However, striatal [ 123 I]β‐CIT binding usually increases with SSRIs via an unknown mechanism. The decrease observed indicates that sertraline also binds to DAT. These results reinforce prior findings that therapeutic doses of SSRIs saturate SERT and suggest that sertraline 150mg is the only SSRI with minimal DAT occupancy. Clinical Pharmacology & Therapeutics (2004) 75 , P20–P20; doi: 10.1016/j.clpt.2003.11.077