5-HTT and 5-HT1A receptor occupancy of the novel substance vortioxetine (Lu AA21004). A PET study in control subjects

  title={5-HTT and 5-HT1A receptor occupancy of the novel substance vortioxetine (Lu AA21004). A PET study in control subjects},
  author={Per Stenkrona and Christer Halldin and Johan Lundberg},
  journal={European Neuropsychopharmacology},

Effect of clinically relevant doses of vortioxetine and citalopram on serotonergic PET markers in the nonhuman primate brain

Comparing its effect to the SSRI citalopram on the binding of [11C]AZ10419369 to the 5-HT1B receptor in the nonhuman primate brain suggests that vortioxetine binds to the5-HT 1B receptor at clinically relevant doses.

Effects of acute and sustained administration of vortioxetine on the serotonin system in the hippocampus: electrophysiological studies in the rat brain

Results indicate that this compound acted as a 5-HT1B receptor partial agonist and decreased the function of terminal 5- HT1B autoreceptor following its sustained administration, which may contribute to the antidepressant effect of vortioxetine.

Vortioxetine: First Global Approval

Animal and in vitro studies indicate that several neurotransmitter systems may be impacted by vortioxetine, with the drug enhancing levels of 5-HT, noradrenaline, dopamine, acetylcholine and histamine in certain areas of the brain, as well as modulating γ-aminobutyric acid and glutamate neurotransmission.

PET studies on the mechanisms of action of antidepressant and antipsychotic drugs

The results suggest that vortioxetine binds to the 5-HT1B receptor when administered at clinically relevant doses, and can be translated into future human studies.

The efficacy of vortioxetine for the treatment of major depressive disorder

This review attempts to compile the efficacy profile of vortioxetine in different clinical trials and the results are compared with other standard antidepressants.

Vortioxetine: a novel antidepressant for the treatment of major depressive disorder

Vortioxetine’s unique psychopharmacological properties might contribute to an improved clinical outcome in MDD patient populations as described in published preclinical and clinical studies and product labels.

Integrated Strategy for Use of Positron Emission Tomography in Nonhuman Primates to Confirm Multitarget Occupancy of Novel Psychotropic Drugs: An Example with AZD3676

The properties of AZD3676 showed preclinical properties consistent with CNS drug potential, including nanomolar receptor affinity and efficacy in rodent models of learning and memory, and these findings support the further integrated use of PET for confirmation of multitarget occupancy of CNS drugs.

Vortioxetine: Clinical Pharmacokinetics and Drug Interactions

Vortioxetine is a novel antidepressant with multimodal activity currently approved for the treatment of major depressive disorder. Vortioxetine is orally administered once daily at 5- to 20-mg doses.



High levels of serotonin transporter occupancy with low-dose clomipramine in comparative occupancy study with fluvoxamine using positron emission tomography.

Clinical doses of clomipramine and fluvoxamine occupied approximately 80% of 5- HTT, and dose escalation would have minimal effect on 5-HTT blockade, and occupational occupancy increased in a curvilinear manner.

Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB positron emission tomography study.

Occupancy of 80% across five SSRIs occurs at minimum therapeutic doses, which suggests that 80% 5-HTT blockade is important for therapeutic effect.

Oral administration of NNC 756 — a placebo controlled PET study of D1-dopamine receptor occupancy and pharmacodynamics in man

The oral dose level of 80 mg should be appropriate to investigate the potential antipsychotic effect of NNC 756, a new benzazepine with high affinity and selectivity for D1-dopamine receptors.

A PET study on regional coexpression of 5-HT1A receptors and 5-HTT in the human brain

The results support a correlation between density levels of the 5-HT1A-receptor and the5-HTT in the raphe nuclei and hippocampus but not in the frontal cortex, which is of particular interest in relation to individual responses to selective serotonin reuptake inhibitor treatment.

Serotonin transporter occupancy with TCAs and SSRIs: a PET study in patients with major depressive disorder

It is supported that TCAs and SSRIs have a shared mechanism of action by inhibition of 5-HTT, and 5- HTT affinity correlated with the recommended clinical dose.

Quantification of 11C-MADAM binding to the serotonin transporter in the human brain.

The suitability of the cerebellum as a reference region for nonspecific (11)C-MADAM binding could be confirmed, thus paving the way for experimentally less demanding approaches, such as the simplified reference tissue model, for applied clinical studies.

PET tracers for 5-HT(1A) receptors and uses thereof.

Imaging the serotonin transporter during major depressive disorder and antidepressant treatment.

  • J. Meyer
  • Psychology
    Journal of psychiatry & neuroscience : JPN
  • 2007
5-HTT imaging findings for understanding major depressive disorder and antidepressant treatment will be discussed, and a strong relation between plasma level and occupancy that is not predictable based on affinity alone is discussed.

Quantitative analyses of carbonyl-carbon-11-WAY-100635 binding to central 5-hydroxytryptamine-1A receptors in man.

The suitability of carbonyl-11C-WAY-100635 for research on central 5-HT1A receptors in neuropsychiatric disorders was supported by the observation that the high signals in the neocortex and raphe nuclei can be described using a kinetic analysis with a metabolite-corrected arterial input function.