ArticleBritish journal of pharmacology2008
Prediction of clinical response based on pharmacokinetic/pharmacodynamic models of 5-hydroxytryptamine reuptake inhibitors in mice.
Article in British journal of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- The impact of paroxetine on insulin secretion and sensitivity through AKT/GLUT4 axis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Intranasal Sertraline for the Investigation of Nose-to-Brain Delivery to Mitigate Systemic Exposure.ACS pharmacology & translational science · 2025Article
- Rebound activation of 5-HT neurons following SSRI discontinuation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Modulation of serotonin transporter expression by escitalopram under inflammation.Communications biology · 2024Article
- Mechanisms of SSRI Therapy and Discontinuation.Current topics in behavioral neurosciences · 2024Review
- Continuous home cage monitoring of activity and sleep in mice during repeated paroxetine treatment and discontinuation.Psychopharmacology · 2023Article
- Effect of selective serotonin reuptake inhibitor discontinuation on anxiety-like behaviours in mice.Journal of psychopharmacology (Oxford, England) · 2022Article
- PET as a Translational Tool in Drug Development for Neuroscience Compounds.Clinical pharmacology and therapeutics · 2022Review
- ROS-Scavenging Selenofluoxetine Derivatives InhibitACS omega · 2022Article
- Encapsulated Escitalopram and Paroxetine Intranasal Co-Administration:Frontiers in pharmacology · 2021Article
- Increased 5-HT2C receptor editing predisposes to PTSD-like behaviors and alters BDNF and cytokines signaling.Translational psychiatry · 2019Article
- Sertraline Delivered in Phosphatidylserine Liposomes Is Effective in an Experimental Model of Visceral Leishmaniasis.Frontiers in cellular and infection microbiology · 2019Article
- Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA).Psychopharmacology · 2017Article
- Comparative effects of sertraline, haloperidol or olanzapine treatments on ketamine-induced changes in mouse behaviours.Metabolic brain disease · 2017Article
- The interaction of escitalopram and R-citalopram at the human serotonin transporter investigated in the mouse.Psychopharmacology · 2014Article
- Vortioxetine restores reversal learning impaired by 5-HT depletion or chronic intermittent cold stress in rats.The international journal of neuropsychopharmacology · 2014Article
- Changes in intensity of serotonin syndrome caused by adverse interaction between monoamine oxidase inhibitors and serotonin reuptake blockers.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Article
- Understanding the hysteresis loop conundrum in pharmacokinetic/pharmacodynamic relationships.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2014Article
- Prenatal exposure to escitalopram and/or stress in rats: a prenatal stress model of maternal depression and its treatment.Psychopharmacology · 2013Article
- Fast-scan cyclic voltammetry analysis of dynamic serotonin reponses to acute escitalopram.ACS chemical neuroscience · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeBridging the gap between preclinical research and clinical trials is vital for drug development. Predicting clinically relevant steady-state drug concentrations (Css) in serum from preclinical animal models may facilitate this transition. Here we used a pharmacokinetic/pharmacodynamic (PK/PD) modelling approach to evaluate the predictive validity of 5-hydroxytryptamine (5-HT; serotonin) transporter (SERT) occupancy and 5-hydroxytryptophan (5-HTP)-potentiated behavioral syndrome induced by 5-HT reuptake inhibitor (SRI) antidepressants in mice. EXPERIMENTAL APPROACH: Serum and whole brain drug concentrations, cortical SERT occupancy and 5-HTP-potentiated behavioral syndrome were measured over 6 h after a single subcutaneous injection of escitalopram, paroxetine or sertraline. [(3)H]2-(2-dimethylaminomethylphenylsulphanyl)-5-methyl-phenylamine ([(3)H]MADAM) was used to assess SERT occupancy. For PK/PD modelling, an effect-compartment model was applied to collapse the hysteresis and predict the steady-state relationship between drug exposure and PD response. KEY
resultsThe predicted Css for escitalopram, paroxetine and sertraline at 80% SERT occupancy in mice are 18 ng mL(-1), 18 ng mL(-1) and 24 ng mL(-1), respectively, with corresponding responses in the 5-HTP behavioral model being between 20-40% of the maximum. CONCLUSIONS AND IMPLICATIONS: Therapeutically effective SERT occupancy for SRIs in depressed patients is approximately 80%, and the corresponding plasma Css are 6-21 ng mL(-1), 21-95 ng mL(-1) and 20-48 ng mL(-1) for escitalopram, paroxetine and sertraline, respectively. Thus, PK/PD modelling using SERT occupancy and 5-HTP-potentiated behavioral syndrome as response markers in mice may be a useful tool to predict clinically relevant plasma Css values.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.