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Assessment of Ketamine Binding of the Serotonin Transporter in Humans with Positron Emission Tomography. | LitMetric

AI Article Synopsis

  • This study investigates the binding of ketamine to the serotonin transporter in humans, which is important for understanding its potential antidepressant effects.
  • Twelve healthy subjects underwent positron emission tomography (PET) scans before and after receiving a standard intravenous dose of ketamine to measure its effects on serotonin transporter occupancy.
  • The results showed that ketamine had less than 10% occupancy of the serotonin transporter post-administration, suggesting that its antidepressant mechanism may differ from traditional antidepressants, which typically show much higher occupancy levels.

Article Abstract

Background: Comprehensive description of ketamine's molecular binding profile becomes increasingly pressing as use in real-life patient cohorts widens. Animal studies attribute a significant role in the substance's antidepressant effects to the serotonergic system. The serotonin transporter is a highly relevant target in this context, because it is central to depressive pathophysiology and treatment. This is, to our knowledge, the first study investigating ketamine's serotonin transporter binding in vivo in humans.

Methods: Twelve healthy subjects were assessed twice using [11C]DASB positron emission tomography. A total of 0.50 mg/kg bodyweight ketamine was administered once i.v. prior to the second positron emission tomography scan. Ketamine plasma levels were determined during positron emission tomography. Serotonin transporter nondisplaceable binding potential was computed using a reference region model, and occupancy was calculated for 4 serotonin transporter-rich regions (caudate, putamen, thalamus, midbrain) and a whole-brain region of interest.

Results: After administration of the routine antidepressant dose, ketamine showed <10% occupancy of the serotonin transporter, which is within the test-retest variability of [11C]DASB. A positive correlation between ketamine plasma levels and occupancy was shown.

Conclusions: Measurable occupancy of the serotonin transporter was not detectable after administration of an antidepressant dose of ketamine. This might suggest that ketamine binding of the serotonin transporter is unlikely to be a primary antidepressant mechanism at routine antidepressant doses, as substances that facilitate antidepressant effects via serotonin transporter binding (e.g., selective serotonin reuptake inhibitors) show 70% to 80% occupancy. Administration of high-dose ketamine is widening. Based on the positive relationship we find between ketamine plasma levels and occupancy, there is a need for investigation of ketamine's serotonin transporter binding at higher doses.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793827PMC
http://dx.doi.org/10.1093/ijnp/pyx085DOI Listing

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